Basics Manual

Basics Manual

SYBYL®-X 1.1 Early 2010

1699 South Hanley Rd. St. Louis, MO 63144-2917

Phone: +1.314.647.1099 Fax: +1.314.647.9241 http://www.tripos.com

LEGAL NOTICE SYBYL and related Tripos modules © 1991-2010 Tripos, L.P. All Rights Reserved. Benchware and related Tripos modules © 2005-2010 Tripos, L.P. All Rights Reserved. AUSPYX © 2001-2010 L.P, Inc. All Rights Reserved. Almond © 2003-2010 Molecular Discovery Ltd. All Rights Reserved. AMPAC © 1997-2010 Semichem. All Rights Reserved. AMM-2001 module in AMPAC version 8.16.5 © 2001 Regents of the University of Minnesota. All Rights Reserved. Concord, Confort, CombiLibMaker, DiverseSolutions, ProtoPlex and StereoPlex © 1987-2001 University of Texas at Austin. All Rights Reserved. FlexX, FlexX-Pharm, FlexE, and FlexS © 1993-2010 BioSolveIT. All Rights Reserved. FUGUE, JOY, HOMSTRAD, ORCHESTRAR © 2010 Cambridge University Technical Services, Cambridge, England. All Rights Reserved. RACHEL © 2002-2010 Drug Design Methodologies. Surflex, Surflex-Dock, and Surflex-Sim © 1998-2010 BioPharmics LLC. All Rights Reserved. VolSurf and Almond © 2001-2010 Molecular Discovery Ltd. All Rights Reserved. Portions copyright 1992-2010 FairCom Corporation. All Rights Reserved. This material contains confidential and proprietary information of Tripos, L.P. and third parties furnished under the Tripos Software License Agreement. This material may be copied only as necessary for a Licensee’s internal use consistent with the Agreement. The allowed use includes printing of hardcopy versions hereof as minimally necessary for Licensee’s internal use. Neither Tripos, L.P., nor any person acting on its behalf, makes any warranty or representation, expressed or implied, with respect to the accuracy, completeness, or usefulness of the material contained in this manual or in the corresponding electronic documentation, nor in the programs or data described herein. Tripos, L.P. assumes no responsibility nor liability with respect to the use of this manual, any materials contained herein, or programs described herein, or for any damages resulting from the use of any of the above. Except for printing of hardcopy versions as stated, no part of this manual may be reproduced in any form or by any means without permission in writing from Tripos (DE), Inc., 1699 South Hanley Road, St. Louis, Missouri 63144-2917, USA (314-647-1099). Selected software programs for methodologies contained or documented herein are covered by one or more of the following patents: Comparative Molecular Field Analysis (CoMFA): US 5,025,388; US 5,307,287; US 5,751,605; AT E150883; BE 0592421; CH 0592421; DE 691 25 300 T2; FR 0592421; GB 0592421; IT 0592421; NL 0592421; SE 0592421. HQSAR: US 6,208,942. Embedded NLM: US 6,675,103. Topomers: US 6,185,506; US 6,240,374; US 7,184,893; US 7,212,951. TopCoMFA: US 7,329,222. DBTop: US 7,330,793. OptiSim: US 6,535,819. Surflex software programs for chemical analysis by morphological similarity: US 6,470,305 B1. SYBYL, UNITY, CoMFA, CombiFlexX, Concord, DiverseSolutions, GALAHAD, LeapFrog, OptDesign, StereoPlex, and Alchemy are registered trademarks of Tripos, L.P. AUSPYX, Benchware, CScore, DISCOtech, Distill, GASP, HQSAR, Legion, MOLCAD, Molecular Spreadsheet, Muse, OptiDock, OptiSim, Pantheon, ProTable, ProtoPlex, Selector, SiteID, Topomer CoMFA, Topomer Search, Tuplets, and Tripos Bookshelf are trademarks of Tripos, L.P. RACHEL is a trademark of Drug Design Methodologies. Surflex, Surflex-Dock, and Surflex-Sim are trademarks of BioPharmics LLC. “FairCom” and “c-tree Plus” are trademarks of FairCom Corporation and are registered in the United States and other countries. All other trademarks are the sole property of their respective owners.

SYBYL Basics Table of Contents Chapter 1. Introduction to SYBYL Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1.1 License Requirements for SYBYL Basics . . . . . . . . . . . . . . . . . . . . . . . . . 8 1.2 What is New with SYBYL Basics Features . . . . . . . . . . . . . . . . . . . . . . . 9 Chapter 2. Quick Introduction to SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.1 Start SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.2 Load Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.3 Rotate, Translate, and Scale Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.4 Save a Molecule to a File . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.5 Get Help . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.6 Exit SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.7 Starting SYBYL and Setting its Environment . . . . . . . . . . . . . . . . . . . . . 23 Chapter 3. The SYBYL Window . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.1 The SYBYL Menubar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.2 The SYBYL Toolbar Icons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3.3 The SYBYL Textports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3.4 Special Keyboard Keys . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Chapter 4. Open and Save Files of Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 4.1 Open Files via the Menubar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4.2 Save a Molecule File via the Menubar . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4.3 Open/Save Mol2 Files via the Command Line . . . . . . . . . . . . . . . . . . . . 41 4.4 Open and Save in Other Formats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 4.5 Convert Between Molecular File Formats . . . . . . . . . . . . . . . . . . . . . . . . 44 4.6 View and Edit Text Files in SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Chapter 5. Understand Molecule and Display Areas . . . . . . . . . . . . . . . . . . . . . . 51 5.1 What are Molecule and Display Areas? . . . . . . . . . . . . . . . . . . . . . . . . . 52 5.2 Change the Default Molecule Area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 5.3 Copy Between Molecule Areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 5.4 Merge Molecule Areas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Chapter 6. Select Atoms, Bonds, or Substructures . . . . . . . . . . . . . . . . . . . . . . . 61 6.1 Selecting With the Mouse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.2 The Selection Menu and Icons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

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6.3 General Description of the Expression Dialogs . . . . . . . . . . . . . . . . . . . . 67 6.4 How to Use the Atom Expression Dialog . . . . . . . . . . . . . . . . . . . . . . . . 75 6.5 How to Use the Bond Expression dialog . . . . . . . . . . . . . . . . . . . . . . . . . 82 6.6 How to Use the Substructure Expression Dialog . . . . . . . . . . . . . . . . . . . 85 Chapter 7. Clear and Reset the SYBYL Display . . . . . . . . . . . . . . . . . . . . . . . . . . .89 7.1 Clear the Screen and Delete Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 7.2 Reset Scaling, Translation, and Rotation . . . . . . . . . . . . . . . . . . . . . . . . . 93 7.3 Undo the Last Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Chapter 8. Build and Modify Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95 8.1 Sketch a Small Molecule Tutorial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 8.2 Ring Fusion Tutorial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 8.3 Load Fragments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 8.4 Access the Sketcher . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 8.5 Modify Molecules Outside of the Sketcher . . . . . . . . . . . . . . . . . . . . . . 118 8.6 Define and Modify Geometric Features . . . . . . . . . . . . . . . . . . . . . . . . 138 Chapter 9. Geometric Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .147 9.1 Intra-/Intermolecular Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 9.2 List Coordinates, Distances, or Angles . . . . . . . . . . . . . . . . . . . . . . . . . 149 9.3 Measure the Intramolecular Angle Between Planes . . . . . . . . . . . . . . . 150 9.4 Measurements Specific to UNITY Features . . . . . . . . . . . . . . . . . . . . . 151 Chapter 10. Get Information on SYBYL Objects . . . . . . . . . . . . . . . . . . . . . . . . . .153 10.1 Information on Selected Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 10.2 List Information About SYBYL Objects . . . . . . . . . . . . . . . . . . . . . . . 155 10.3 Print Information About SYBYL Objects . . . . . . . . . . . . . . . . . . . . . . 156 Chapter 11. Use Molecule Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157 11.1 Database Formats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 11.2 Database Tutorial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 11.3 Open and Close SYBYL Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 11.4 Retrieve Molecules from a SYBYL Database . . . . . . . . . . . . . . . . . . . 169 11.5 Obtain Information on Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 11.6 Manage Database Content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 11.7 Save Database Molecules to Mol2 Files . . . . . . . . . . . . . . . . . . . . . . . 178 11.8 Database Qualifiers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

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11.9 The DATABASE Command . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 11.10 System Utilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 Chapter 12. Manage SYBYL Sessions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 12.1 Save a SYBYL Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 12.2 Open (Restore) a Saved Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 12.3 Delete a Saved Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 12.4 Open a New Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 12.5 Close a SYBYL Session . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 12.6 Record and Play Back SYBYL Operations . . . . . . . . . . . . . . . . . . . . . 191 Chapter 13. SYBYL Objects and Their Expressions . . . . . . . . . . . . . . . . . . . . . . . 197 13.1 Definitions of SYBYL Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 13.2 Formats for Specifying Objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 13.3 Create Complex Expressions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 Chapter 14. Sets in SYBYL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 14.1 Global Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 14.2 Local Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 14.3 Dynamic Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222 14.4 Built-in Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 14.5 Static Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 14.6 Working with Sets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 Chapter 15. Libraries of Chemical Groups and Fragments . . . . . . . . . . . . . . . . . 231 15.1 Group Library Structure and Contents . . . . . . . . . . . . . . . . . . . . . . . . . 232 15.2 Fragment Library Structure and Contents . . . . . . . . . . . . . . . . . . . . . . 233 Chapter 16. Advanced SYBYL Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 16.1 Automatic Command Execution at SYBYL Startup . . . . . . . . . . . . . . 238 16.2 Execute a SYBYL Command on Multiple Molecules . . . . . . . . . . . . . 239 16.3 Define Markush Atoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

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Chapter 1.

Introduction to SYBYL Basics SYBYL uses computer analysis to assist in the description and prediction of molecular behavior. SYBYL Base includes the basic tools for molecular modeling. Topics in this manual include: •

Quick Introduction to SYBYL on page 13

•

Rotate, Translate, and Scale Molecules on page 17

•

The SYBYL Window on page 25

•

Open and Save Files of Molecules on page 33

•

Understand Molecule and Display Areas on page 51

•

Select Atoms, Bonds, or Substructures on page 61

•

Clear and Reset the SYBYL Display on page 89

•

Build and Modify Molecules on page 95

•

Geometric Measurements on page 147

•

Get Information on SYBYL Objects on page 153

•

Use Molecule Databases on page 157

•

Manage SYBYL Sessions on page 183

•

SYBYL Objects and Their Expressions on page 197

•

Sets in SYBYL on page 215

When combined with SYBYL applications, SYBYL Base provides a completely integrated environment for computational chemistry and molecular modeling.

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Chapter 1. Introduction to SYBYL Basics License Requirements for SYBYL Basics

1.1 License Requirements for SYBYL Basics Consolidated Licensing SYBYL-X introduced a simplified licensing scheme in which the “SYBYL” license provides access to all functionality described in this manual. Two additional keys perform the following functions: •

SYBYL_Interactive: Controls interactive access to SYBYL and other programs

•

CPU: Allows batch operations

Module-Based Licensing SYBYL continues to run with a license file issued before the SYBYL-X release. The functionality described in this manual requires a “SybylBasic” license. Additionally, a “BioPolymer” license:

8

•

is required to assign and label AMBER and Kollman atom types;

•

is used, if present, to add hydrogens to proteins, nucleic acids and saccharides.

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Chapter 1. Introduction to SYBYL Basics What is New with SYBYL Basics Features

1.2 What is New with SYBYL Basics Features New and Modified Functionality New in SYBYL-X 1.1 Explore the new selection model: •

Select any atom or surface by simply clicking on it. Double-dick an atom to select the substructure, triple-click to select the entire molecule. Ctrl-Alt and drag to select atoms in a rectangular area.

•

More about Selecting With the Mouse.

•

Most functionality has been modified to work on pre-selected atoms or entire molecule areas. Discover The Selection Menu and Icons.

New toolbars provide easy access to a vast array of display functions without the need for dialogs, reducing the number of mouse clicks for basic operations. •

Each toolbar may be repositioned and customized.

•

Discover The SYBYL Toolbar Icons.

Atom rendering is now part of the molecular description and no longer a background image. Mix the rendering styles within a molecule to highlight regions of interest by, for example applying spacefill to the metals and capped sticks to the ligand. Rendering styles are saved in Mol2 and session files. The SYBYL Window SYBYL-X introduced a new, modern look: •

The command console is now docked into the main window. An additional message area receives the text output of system operations.

•

It is now possible to navigate within the menu and dialogs via keyboard hot keys and the mouse’s scroll wheel.

•

All dialogs may be closed by clicking the X in the corner of their window.

•

The F1 keys launches the Tripos Bookshelf, SYBYL’s online Help.

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Expression Dialog Redesign The various expression dialogs (Atom Expression, Bond Expression, etc.) and subdialogs have been significantly redesigned. Some of the changes include: •

A hierarchical listing of items that can be expanded and collapsed as needed. This hierarchy provides easy multi-item selection (e.g., clicking a substructure name automatically selects all atoms in that substructure).

•

A right-click menu in the hierarchy contains options for inverting the selection within a substructure, within a chain, or within the entire molecule, where applicable.

•

There are partial selection indicators (grey check marks versus bold check marks) to help you identify when, for example, some but not all atoms of a substructure are selected.

•

Boolean operations on selected sets of items are now accomplished by defining both sets first and then specifying the Boolean operation.

See the Expression dialog description for more information. [SYBYL-X] New Look for the SYBYL Sketcher The SYBYL Sketcher (Edit > Sketch Molecule) is driven by a set of toolbars. [SYBYL-X] •

Sketcher functions

•

Atomic symbols, with access to the full periodic table

•

Groups, as defined in the Group Library. Note that a group can only be added to an existing atom.

Note that, with this new design, loading fragments and changing Tailor settings (e.g., clean up methods) must now be made before accessing the Sketcher. The Sketcher operates on different molecule areas depending on atom selection: •

To modify an existing molecule you must select one of its atoms before invoking the Sketcher.

•

To sketch a new molecule, clear all selection then invoke the Sketcher. The new molecule will be sketched in the first, empty molecule area.

Pseudo-atoms The ability to define pseudo-atoms is once again available. It places dummy atoms at the centroid positions of prochiral, methyl, and phenyl ring groups. See Add Pseudo-atoms (Centroids) on page 119. [8.1]

10

•

Edit > Add > Pseudo-atoms

•

ADD_PSEUDOATOMS mol_area

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Reading .sd Files Files with the .sd extension can beloaded directly from the Open File dialog. [SYBYL-X]

Known Limitations DATABASE If your machine is on a network and has only the NFS client operating system software installed (i.e., not the NFS server software itself), a SYBYL session running on that machine will fail to open databases residing on NFS mounted disks connected to a remote machine. When you try to open a database, you will get a CANT_GET_LOCK error. Install the NFS server operating system software to fix the problem. This problem does not occur if your machine is completely stand-alone or if you have the NFS server operating system software installed.

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Chapter 2.

Quick Introduction to SYBYL Run this tutorial to learn some basics operations in SYBYL: •

Start SYBYL on page 13

•

Load Molecules on page 16

•

Change the Display on page 16

•


•

Save a Molecule to a File on page 20

•

Get Help on page 21

•

Exit SYBYL on page 22

•

Starting SYBYL and Setting its Environment on page 23

A Matter of Time: This tutorial requires about 5 minutes of personal time.

2.1 Start SYBYL Windows Users:

¾

Double-click the SYBYL-X 1.1 icon on your desktop or find SYBYL-X 1.1 in your computer’s All Programs list.

Linux Users:

¾

If there is a SYBYL-X 1.1 icon on your desktop, double-click it. Otherwise open a system shell.

Start the SYBYL program using Trigo:

¾

At the system prompt type: trigo sybylx1.1

SYBYL Session A SYBYL session begins when you start SYBYL and ends when you close it. The current state of a SYBYL session can be saved and reloaded at a later time. You may also run multiple sessions simultaneously. See Manage SYBYL Sessions on page 183 for more details.

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Chapter 2. Quick Introduction to SYBYL Start SYBYL

Explore the SYBYL Window The SYBYL graphical interface is composed of a menubar, toolbar icons, a graphics area, and a text console.

Menubar A SYBYL menu option can: •

be a simple command: Edit > Delete Everything

•

lead to submenus: Biopolymer > Model Proteins > ORCHESTRAR

•

open a dialog: File > Import File...

Each list of menu options can be detached from the menubar so that it remains visible even after a selection is made. •

To detach a menu: click the dashed line above the first item.

•

To close a tear-off: click the X in the upper right corner.

When you initiate an operation by clicking a menu item, no other operation is possible until either that operation completes or you cancel it. All menubars are greyed out while the current operation is active.

14

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Chapter 2. Quick Introduction to SYBYL Start SYBYL

Additional Information: •

The SYBYL Menubar on page 26

•

Menu, Dialog, and Mouse Shortcuts on page 27

Toolbars Use the icons in the SYBYL toolbars to interact with the graphics. Clicking some icons immediately performs an action, others require a selection to be made from a pull-down, and others display a tool that can remain open as you work or can be closed by pressing the X button in the corner of its window. Command Console Use this console to enter any command at the SYBYL command prompt (SYBYL>). After entering a command, the system performs the command operation and redisplays the SYBYL command prompt. See the List of SYBYL Commands in the Reference Guide. Note: The menubar and command line are available simultaneously. System Messages A few SYBYL operations report information in this area. You may also type simple system commands in the Command Console (e.g. cmd ls to list the files in the current directory or folder). The output of such a command appears in the System Messages area. See The SYBYL Window on page 25 for more in-depth description or the SYBYL interface.

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Chapter 2. Quick Introduction to SYBYL Load Molecules

2.2 Load Molecules Molecules can be loaded into SYBYL from files. A Fragment Library is also available, containing a number of small, mostly cyclic, molecules.

2.2.1 Load a Molecule from a File: Read in dicloxacillin from a list of demo files distributed with SYBYL.

¾ ¾

File > Import File (

)

In the Open File dialog, click [$TA_DEMO] in the Bookmarks section on the left.

The contents of SYBYL’s demo directory are displayed in the sections on the right.

¾ ¾

Select example.mdb in the Directory Navigation list in the center. Select dicloxacillin.mol2 in the Selection list on the right then press OK.

SYBYL loads dicloxacillin into M1, the default molecule area if you started with a blank screen. A molecule area is a region of memory that holds a particular molecule.

2.2.2 Load a Molecule from the Fragment Library: Load vitamin B2.

¾ ¾

File > Get Fragment Select VITAMIN B2 in the list of available molecules and press OK.

SYBYL loads vitamin B2 into M2, the first empty molecule area. Both molecules are displayed in the center of the SYBYL window. In the next section, you will learn how to change the display so that you can see the molecules more clearly.

2.2.3 Change the Display 1. Change the display so you can see the molecules side-by-side.

¾

16

Click

SYBYL Basics

on the Display toolbar and select Half.

SYBYL-X 1.1

Chapter 2. Quick Introduction to SYBYL Rotate, Translate, and Scale Molecules

SYBYL displays the molecules in display areas D1 (right) and D2 (left). For more information, see What are Molecule and Display Areas? on page 52. 2. Toggle the display for each molecule off and on.

¾ ¾

Click

on the Molecule toolbar.

In Molecule Display Options dialog, for row M1, toggle the check box in the Mol Vis column off and then on.

Notice also that the check box appearance changes. Watch the SYBYL screen when you toggle the display off and on. Likewise, the other molecule can be displayed and undisplayed using the respective check box.

¾

Display both molecules and click the X in the upper corner to close the dialog.

2.3 Rotate, Translate, and Scale Molecules Structure rotation is based on the Cartesian coordinate system such that the X-axis is horizontal, the Y-axis is vertical, and the Z-axis is perpendicular to the viewer. SYBYL supports a three-button mouse, reserving the right button for context sensitive menus. When using a touch pad use

on the Mouse Mode toolbar.

2.3.1 Move All Objects Together Move All Objects

Mouse

Keyboard

X,Y rotation X,Y translation

Left Middle Left Left Middle —

— Shift Ctrl+Shift Ctrl Ctrl+arrow keys

Z rotation Z translation 90° rotationa

a. To change the rotation increment from its default of 90°: TAILOR SET GRAPHICS KEYBOARD_ARROW_ROTATION.

Linux Usage Note If the Ctrl or Alt keys do not behave as described above it may be because of a preference setting for your window manager. We recommend the following setting for the Gnome window manager:

SYBYL-X 1.1

SYBYL Basics

17


•

System (or Applications) > Preference > Windows

•

Set Movement Key to Super (or “Windows logo”).

1. Rotate both molecules. When you start a SYBYL session all images on the screen are affected simultaneously by rotations and translations.

¾

With the cursor in the graphics window, press the left mouse button and move your mouse in any direction. Notice that all molecules move. This is because your current mouse focus setting is G (global), as indicated by the toolbar.

icon on the Mouse Mode

2. Rotate the molecules about the Z-axis.

¾

Simultaneously hold down the Ctrl and Shift keys while pressing the left button and dragging left or right.

2.3.2 Move Selected Objects Only To move one or more, but not all, objects simultaneously you must first select them. Then add Alt to the key/mouse combination: Move Selected Objects

Mouse

Keyboard

X,Y rotation X,Y translation

Left Middle Left Left

Alt Alt Alt+Shift Alt+Ctrl+Shift Rotate all objects in X,Y by 90° then select the object(s) of interest and translate them in the XY plane.

Z rotation Z translation

3. Move dicloxacillin to the upper right corner.

¾ ¾

Click an atom in dicloxacillin. Hold down the Alt and Shift keys while pressing the left button and dragging the cursor to the upper right corner of the display area. Vitamin B2 remains stationary.

An alternative method is to change the mouse focus using a toolbar icon.

¾

18

Clear the selection first by clicking

SYBYL Basics

on the Selection toolbar.

SYBYL-X 1.1


¾

Click

on the Mouse Mode toolbar.

SYBYL opens the Mouse Focus Options dialog with a list of molecules.

¾

Click M1 dicloxacillin. SYBYL changes the mouse focus to M1. Note that the notation on the icon changed from G to M1. This notation represents the active object for the mouse focus.

¾

Middle-click and drag dicloxacillin to the lower right corner. If you had multiple molecules in D1, all of those molecules would move together. In such cases, to only move a particular molecule using this dialog, click the name of the molecule in the list, then use the mouse.

4. Move vitamin B2 to the upper left corner.

¾

In the dialog click M2 vitamin B2. SYBYL changes the mouse focus to M2 only.

¾ ¾

Middle-click and drag vitamin B2 to the upper left corner. Reset the mouse focus to Global then click X in the upper corner to close the Mouse Focus Options dialog.

2.3.3 Zoom Objects with the Mouse The zoom modifies the scale of all objects, whether visible or not. Mouse

Zooming Action

Wheel

Scroll forward to zoom in by 5%. Scroll backward to zoom out by 5%. Drag the mouse to the upper right to zoom in. Drag the mouse to the lower left to zoom out.

Left+Middle or Ctrl+Left

5. Modify the size of the molecules.

¾

Use the mouse’s scroll wheel to increase the size of both molecules.

If your mouse does not have a scroll wheel use either of the alternatives described above.

SYBYL-X 1.1

SYBYL Basics

19

Chapter 2. Quick Introduction to SYBYL Save a Molecule to a File

2.3.4 Reset Rotation, Translation, and Scale All rotations, translations, and scale operations applied globally or individually can be reset with a single click.

¾

Click

.

2.3.5 Moving Objects in a Single Display Area If you have four or fewer molecules in different display areas and you want to manipulate one of them independently of the others you can toggle the mouse focus between Global (all together) and a single one by pressing a function key. The label of the Mouse Focus icon (

¾ ¾

) will reflect the current status.

•

F9—toggles between Global and D1

•

F10—toggles between G and D2

•

F11—toggles between G and D3

•

F12—toggles between G and D4 Experiment with function keys F9 and F10 to move each molecule independently of the other, then both together. Be sure to toggle the function keys back to Global when you are done.

2.4 Save a Molecule to a File ¾

File > Export File (

)

SYBYL opens the Save Molecule dialog.

¾ ¾ ¾

Verify that m1: dicloxacillin is highlighted in the list; if not, select it. Type diclox_tut in the File field. Press Save.

SYBYL creates a file named diclox_tut.mol2 in your current directory. Note: You can select multiple structures and save them in a specified format. For more information, see Save a Molecule File via the Menubar on page 39.

20

SYBYL Basics

SYBYL-X 1.1

Chapter 2. Quick Introduction to SYBYL Get Help

2.5 Get Help To learn about a specific feature or dialog: •

Press the keyboard F1 key.

•

Press the Help button in any dialog.

•

Select Help on the SYBYL menubar.

•

Type HELP in the console.

The Tripos Bookshelf is SYBYL’s complete online documentation. It is organized by SYBYL application and consists of: •

HTML-style pages that provide context-sensitive help within the software. To ensure easy navigation, each page is linked to the table of contents and the index of the book it belongs to as well as to the Tripos Bookshelf’s main page. It is also equipped with a bread crumb locator.

•

PDF copies of all the manuals. The “View or Print” link in each Bookshelf topic’s main page gives you access to the complete documentation for that topic in PDF format.

•

A full text search engine.

2.5.1 Search for Specific Information To use the search engine click the Search tab then type the text you want to look for in the search box and click Search or press the Enter key on your keyboard. The list of documents found is ordered by decreasing number of occurrences of the search text. To access the documentation independently of the SYBYL application, direct your favorite web browser to TriposBookshelf/index.html within your SYBYL installation.

2.5.2 SYBYL Version and Local System Information Help > About SYBYL A dialog provides the following information: •

The SYBYL version, platform type, and creation date.

•

The copyright notice.

•

Your Server Host ID number. After registering to the Tripos Web site, enter this number in your profile to gain access to the SYBYL software download section.

SYBYL-X 1.1

SYBYL Basics

21

Chapter 2. Quick Introduction to SYBYL Exit SYBYL

•

A System Info button presents more detailed information in the System Messages area. This information is useful when you contact your Tripos Support office.

2.6 Exit SYBYL Exiting SYBYL means closing the SYBYL session. If you have multiple sessions open simultaneously you must close each of them individually.

2.6.1 How to Exit SYBYL Exit SYBYL in any of the following manners: From the Menubar: File > Exit When exiting SYBYL via the menubar you will be prompted whether to save the current session. If you choose not to save a session upon exit you will be prompted whether to save molecules and spreadsheet that have not been saved after the most recent modification. In the Console: Type: exit or quit. When exiting SYBYL at the command line you will not be prompted whether to save the session. You will be prompted whether to save molecules and spreadsheet that have not been saved after the most recent modification.

2.6.2 End the Tutorial

¾

File > Exit

You are presented with the opportunity to save the session. A SYBYL session ends when SYBYL is exited. The current state of a SYBYL session can be saved and reloaded at a later time. See Manage SYBYL Sessions on page 183 for more details. If you choose not to save a session upon exit you will be prompted whether to save molecules and spreadsheet that have not been saved after the most recent modification. For this tutorial, do not save the session.

¾

Click Don’t Save.

SYBYL closes.

22

SYBYL Basics

SYBYL-X 1.1

Chapter 2. Quick Introduction to SYBYL Starting SYBYL and Setting its Environment

2.7 Starting SYBYL and Setting its Environment There are several ways to access SYBYL. Each serves a different purpose. You will find all access modes on the SYBYL-X 1.1 look-aside menu in your computer’s list of programs or applications.

2.7.1 Standard SYBYL-X Startup The easiest way to start SYBYL is via the desktop icon, there during software installation.

, if it was placed

The standard SYBYL application includes a menubar, toolbars, a graphics window, a command console, and a system messages area. See The SYBYL Window on page 25 for a full description. If there is no SYBYL icon on your desktop, launch SYBYL as follows: Windows: •

All Programs > SYBYL-X 1.1 > SYBYL-X

Linux: •

Applications menu > SYBYL-X 1.1 > SYBYL-X

•

Or, in a system shell, type: trigo sybylx1.1

2.7.2 SYBYL-X Plus Console You may start SYBYL with an additional, separate system console. Although you may not type in this console, a small amount of information will be directed to it by most SYBYL “db” commands (described in the UNITY Manual). Information in this console may be useful for debugging purpose. To launch SYBYL with the additional system console: Windows: •

All Programs > SYBYL-X1.1 > SYBYL-X Plus Console

Linux: •

SYBYL-X 1.1

Applications menu > SYBYL-X1.1 > SYBYL-X Plus Console

SYBYL Basics

23

Chapter 2. Quick Introduction to SYBYL Starting SYBYL and Setting its Environment

•

Or, in a system shell, type: trigo -shell sybylx1.1 sybyl -xterm

2.7.3 SYBYL-X Command Line You may start SYBYL for use of its command line operations only. In this mode only the command console is available. The SYBYL graphics window, menubar and toolbars are not displayed. To launch SYBYL in command mode only, without the graphics window: Windows: •

All Programs > SYBYL-X1.1 > SYBYL-X Text Console

Linux: •

Applications menu > SYBYL-X1.1 > SYBYL-X Text Console

•

Or, in a system shell, type: trigo -shell sybylx1.1 sybyl -text

2.7.4 SYBYL-X Environment Shell A large number of applications that are accessible from within SYBYL may also be run in standalone mode. Examples of these are the “db” commands (UNITY Manual), Surflex-Dock and Surflex-Sim, among others. All that is required to run these applications is a system shell in which SYBYL’s environment variables have been defined. To open a system shell in which the SYBYL environment has been defined: Windows: •

All Programs > SYBYL-X1.1 > SYBYL-X Environment Shell

Linux:

24

•

Applications menu > SYBYL-X1.1 > SYBYL-X Environment Shell

•

Or, in a system shell, type: trigo -shell sybylx1.1

SYBYL Basics

SYBYL-X 1.1

Chapter 3.

The SYBYL Window When SYBYL starts its main window is presented. The graphics window contains the menubar, toolbar icons, and the display area. The console is docked below the display area. All layout changes you make are preserved in .sybyl/windowState within your home directory or folder.

•

The SYBYL Menubar on page 26 •

SYBYL Menus

•

Menu, Dialog, and Mouse Shortcuts

•

The SYBYL Toolbar Icons on page 29

•

The SYBYL Textports on page 30

•

Special Keyboard Keys on page 32

SYBYL-X 1.1

SYBYL Basics

25

Chapter 3. The SYBYL Window The SYBYL Menubar

3.1 The SYBYL Menubar A SYBYL menu option can: •

be a simple command: Edit > Delete Everything

•

lead to submenus: View > Hydrogen Bonds > Intermolecular

•

open a dialog: File > Open Session...

When you initiate an operation by clicking a menu item, no other operation is possible until either that operation has finished or until you cancel it. All menubars are greyed out while the current operation is active.

3.1.1 SYBYL Menus Each list of menu options can be detached from the menubar so that it remains visible even after a selection is made. •

To detach a menu: click the dashed line above the first item.

•

To close a tear-off: click the X in the upper right corner.

File

Edit

View

Compute

Applications

Biopolymer

26

SYBYL Basics

Contains options to load information for display in SYBYL. It also has options for operations such as saving files, creating Molecular Spreadsheets, editing text files, managing sessions, and exiting SYBYL. Focus on creating and modifying structures in the SYBYL display. It contains options for operations such as clearing the screen, sketching, modifying, copying, merging, and extracting structures. Options affecting the visualization of structures in the SYBYL display. It contains options for operations such as coloring, labeling, hiding, managing backgrounds, surfaces, and monitors and accessing the 2D Viewer. Tools for measuring are also found here. SYBYL’s minimization and dynamics tools can be accessed. It contains options for calculating charges, loading force field parameters and conformational searches. This menu also contains options for analyzing the results of the calculations, defining aggregates, and defining constraints. Accessing the specialized tools and techniques offered by Tripos for use in SYBYL. Tools for matching and fitting are also found here. Functionality specific to biopolymer structures

SYBYL-X 1.1


UNITY Options

Help

Tools for performing various types of database searches. Access to the interface for setting tailor variables. The default molecule area and directory can be changed from this menu and various lists and information can be obtained. Functionality for recording and playing back command sequences is also available. Options for accessing the Tripos Bookshelf (HTML version of the SYBYL documentation). Release notes and other information about the current version are also available from this menu.

See the SYBYL Menubar to Command Mapping (accessible from the Tripos Bookshelf’s main page) to find a complete listing of options for each menu item, with links to descriptions and corresponding commands.

3.1.2 Menu, Dialog, and Mouse Shortcuts Menu Shortcuts You can navigate within the SYBYL menu use the keyboard. 1. Press the keyboard Alt key while typing the underlined letter corresponding to the menu of interest. For example, Alt-E opens the Edit menu. 2. Once a menu is open: •

Simply type the underlined letter associated with the item of interest.

•

Use the keyboard arrow keys to navigate within the menu.

•

Press the keyboard Enter key to activate the highlighted menu item.

Dialog Shortcuts Within a dialog: •

Press the keyboard Tab key to skip to the next field or item in a list.

•

Use the keyboard arrow keys to move up or down in a list.

•

Use the mouse’s scroll wheel to select an item in a pull-down menu or to move a slider’s position.

•

In a dialog containing a single list of option, double-click an item to select the option and close the dialog.

SYBYL-X 1.1

SYBYL Basics

27


Where is the dialog? If SYBYL seems unresponsive, it may be because the active dialog has become hidden by another window. Click (stack windows) to bring the active window in front of the display area. Mouse Shortcuts The following shortcuts involve the mouse: •

If your mouse has a scroll wheel you can use it in the graphics area to zoom in and out. This scaling action applies to all objects, whether visible or temporarily hidden.

•

Right-click on the following objects to display relevant context menus: •

an atom

•

a surface or ribbon

•

the SYBYL backdrop

Use the mouse with keyboard keys to make selections and to move objects.

28

•

Selecting With the Mouse on page 62

•


SYBYL Basics

SYBYL-X 1.1

Chapter 3. The SYBYL Window The SYBYL Toolbar Icons

3.2 The SYBYL Toolbar Icons Use the icons in the SYBYL toolbars to interact with the graphics. A toolbar can be docked under the menubar or to either side of the display area or it can be “torn off” so that it exists as its own window. Simply click the line in front of a group of icons and dragging the toolbar to its new location. To activate an icon, click it. Any dialogs that are displayed can remain open as you work or you can close them by clicking the X in the upper corner or their window. Standard Edit View Display Molecule Selection Transformation Biopolymer Mouse Mode Miscellaneous

SYBYL-X 1.1

SYBYL Basics

29

Chapter 3. The SYBYL Window The SYBYL Textports

3.3 The SYBYL Textports Two text areas are docked within the main SYBYL window, initially below the graphics window. Use the sash to re-apportion the space given to each. 1. Command Console This area contains the interactive SYBYL prompt (SYBYL>). Type any SYBYL command at the prompt to execute it immediately. When the operation completes the SYBYL prompt will reappear. See the List of SYBYL Commands in the Reference Guide. 2. System Messages This area contains the text output of system operations. A few SYBYL functions report information in this area. You may also type simple system commands in the Command Console (e.g. cmd ls to list the files in the current directory or folder). The output of such a command appears in the System Messages area. To detach the command console or the system message area click its icon. To re-dock a detached window, drag its title bar to any edge within the SYBYL graphics window.

3.3.1 Typing Commands in the Console Although most SYBYL functions are available via the menubar and toolbars, you may need or prefer to type some SYBYL commands in the command console. You may enter a command and all its options on a single line. Only the shortest unique string needs to be typed to identify a command or any of its arguments. If you type only the command name then press Enter, you will be prompted for the necessary arguments with default values in angle brackets. SYBYL has two modes for command operations: •

In the standard mode, commands are entered in the console but object selections can also be done via the “expression” dialogs. Pressing the Enter key after each argument will display the appropriate dialog when an object selection is required.

•

You may also switch to a mode in which once a command name has been typed its remaining arguments must be entered in the console

To activate full command mode type: SET PICKING NO_PICKING To return to the standard mode, type: SET PICKING OBJECT_ONLY

30

SYBYL Basics

SYBYL-X 1.1

Chapter 3. The SYBYL Window The SYBYL Textports

3.3.2 Special Characters When interacting with SYBYL in the Command Console use the following characters: •

?—Use the help character at any time to obtain information about a command, the values of an argument, or the format of a specific parameter.

•

^ (caret)—Use the abort character in response to any prompt to terminate the command operation. No changes are made to the molecule(s).

•

| (vertical bar)—Use the end loop character to terminate the entry of parameters being requested in an indefinitely repeating loop. When you have completed all the required entries, respond to the next prompt with the end loop character. SYBYL terminates the request loop and moves on to the next parameter.

SYBYL-X 1.1

SYBYL Basics

31

Chapter 3. The SYBYL Window Special Keyboard Keys

3.4 Special Keyboard Keys Key

Action

F1 F7

Help Toggle hardware stereo on and off. F7 is active only if the necessary hardware is available. See Hardware Stereo in the Installation and Administration Manual. Toggle mouse focus between Global and D1. Toggle between Global and D2. Toggle between Global and D3. Toggle between Global and D4. Rotate all displayed objects +90° about the X-axis. Rotate all displayed objects –90° about the X-axis. Rotate all displayed objects +90° about the Y-axis. Rotate all displayed objects –90° about the Y-axis.

F9 F10 F11 F12 Ctrl + Up arrow Ctrl + Down arrow Ctrl + Left arrow Ctrl + Right arrow

32

SYBYL Basics

SYBYL-X 1.1

Chapter 4.

Open and Save Files of Molecules •

Open Files via the Menubar on page 34

•

Save a Molecule File via the Menubar on page 39

•

Open/Save Mol2 Files via the Command Line on page 41

•

Open and Save in Other Formats on page 42

•

Convert Between Molecular File Formats on page 44

•

View and Edit Text Files in SYBYL on page 49

SYBYL-X 1.1

SYBYL Basics

33

Chapter 4. Open and Save Files of Molecules Open Files via the Menubar

4.1 Open Files via the Menubar The SYBYL file browser presents slight differences depending on context: •

Open a file to import it into SYBYL: File > Import File ( molecule area is often associated with that operation.

). A

•

Open a SYBYL session: File > Open Session ( ). Each saved SYBYL session consists of many files stored in a directory with the .ses extension.

•

Save an image to a file: File > Save Image.

Common Features Directory

34

SYBYL Basics

The currently selected directory. The pull-down provides access to the parent directories.

SYBYL-X 1.1


Toolbar

•

—Go back to the previously selected directory.

•

—Go up one level in the directory tree, that is, the parent directory.

•

—Delete the file(s) selected in the list.

•

Bookmarks

Directory Navigation

Selection

SYBYL-X 1.1

—Create a new directory/folder within the currently selected directory. This button is disabled if you do not have permission to write to the selected directory (e.g. the demo directory). Provides quick access to commonly used directories. By default, the current working directory (identified by the variable $CWD), your home directory (identified as $HOME), and SYBYL’s demo directory (set by the variable $TA_DEMO) are listed. If you changed directory while in SYBYL, the variable $PWD identifies the directory in which you started SYBYL. • To add another directory to the list, navigate to that directory then press the button. • To remove a directory from the list, click that directory and press the button. (Note that the default bookmarks cannot be removed.) User-defined bookmarks are stored and can be directly edited in the $HOME/.sybyl/directory_bookmarks file. Note: You can resize the list of bookmarks by moving the horizontal sash. Select one of the sub-directories if you want to select a file from it. Note: a vertical sash to the right of this list allows you to widen this section of the dialog. List all files of the specified format in the selected directory. You may retrieve multiple files at once by holding the Ctrl key while selecting the desired files.

SYBYL Basics

35


On File > Import File File to read

36

SYBYL Basics

The name(s) of file(s) selected to be read in. You may type a subdirectory name or a full directory path and press OK to list the files it contains. You may also type the name of a file. For MDL SD or MOL files, normalization (aromatization and standardization) of the structures is done by default. To control this default behavior, use the command TAILOR SET TABLE MDL_NORM_AROM. The label for this field varies depending on how this dialog was invoked. For example, if the dialog was displayed using File > Database > Open, this field is labeled Databases.

SYBYL-X 1.1


Files of Type

•

•

•

Molecule—Lists files containing molecules (e.g., .mol2, .pdb, .sln, .hits, . sdf, .cry,…). Selected file(s) will be loaded into molecule areas. Files of type SLN and SD are loaded into spreadsheets. If a Mol2 file contains multiple molecules, you will be given the choice to load the contents into an MSS or separate molecule areas. SYBYL Mol2—Lists files with the .mol2 extension. Selected file(s) will be loaded into molecule areas. If a file contains multiple molecules, the Multi-Mol2 File Detected dialog is displayed asking whether to load the contents into an MSS or molecule areas. SLN—Lists files with the .sln and .hits extensions. Selected file(s) will be loaded into MSSs, one for each file. A file of type SLN must start with the line: #SYBYL/3DB HITLIST

MDL-SDF—Lists only MDL .sdf files; a data format that can contain multiple chemical structures and arbitrary data associated with those structures. Selected file(s) will be loaded into MSSs, one for each file. • PDB—Lists files containing proteins (e.g., .pdb, .ent, …). Selected file(s) will be loaded into molecule areas. • Sequence—Lists files containing sequences (e.g., .pir, .fast). Selected file(s) will be loaded into molecule areas and into the Sequence Viewer. • Spreadsheet—Lists files that can be loaded into a spreadsheet (e.g., .tbl, .tsv, .csv, .hits, .sln, .3db, .sdf, and .chom (created by Legion)). Selected file(s) will be loaded into MSSs, one for each file. • Database—Lists database files (e.g., .tdb, .mdb). Selected file(s) will be loaded into MSSs, one for each file. • Any File—Lists all entries in the selected directory. SMILES files can be selected and opened using this option. Other options may appear in this pull-down depending on how this dialog was invoked and the type of object being opened. •

SYBYL-X 1.1

SYBYL Basics

37


Molecular Areas

List of molecule areas and names of any currently displayed structures. By default, SYBYL automatically selects the first available molecule area. If multiple files are selected, molecules are loaded in consecutive molecule areas. (Note that there are cases when this list is disabled, for example, when opening a database (File > Database > Open)).

On File > Open Session See Manage SYBYL Sessions on page 183 for additional information. Directory

Name of the session directory selected at the top of the dialog.

Files of Type

Session (*.ses)

On File > Save Image See Image - Save to FIle, Copy to Clipboard in the Graphics Manual for additional information. Filename Files of Type

Image Dimensions

JPEG Options

Enter the name of the file to be created. • JPEG File (*.jpg *.jpeg) • Bitmap File (*.bmp) • PNG File (*.png) • TIFF File (*.tif *.tiff) The Width and Height of the image as captured are reported in Inches and Pixels for the specified DPI value (default is 300). You may modify these before saving the image to a file. Note that these values are interdependent and that the proportions will be maintained. After modifying a value, press the Enter key to effect the change. The Quality Slider provides an image compression mechanism.

Additional Information:

38

•

Load Molecules on page 16 for an example exercise.

•


•


•


•

Image - Save to FIle, Copy to Clipboard in the Graphics Manual

SYBYL Basics

SYBYL-X 1.1

Chapter 4. Open and Save Files of Molecules Save a Molecule File via the Menubar

4.2 Save a Molecule File via the Menubar Use the File > Export File ( ) option to save one or more molecules. By default, SYBYL saves the selected molecule(s) in the specified format to the current working directory. What is saved with the file depends on the file type. Only the selected molecules are saved, not associated background images, if any are present.

¾


File

Format

Molecule List

)

Name for the file being saved. You can accept the default, enter a new file name, or specify a different directory via the [...] button. Acceptable file names: • 3 to 15 alphanumeric characters • May include _ (underscore) or a - (hyphen) A default extension for the specified file format will automatically be added to the filename. Therefore, do not include a (.) period in your filename, unless you are entering an extension. Select the file format. Note: You can save multiple structures in a single file when you use Mol2 and MDL-SDF. Use the buttons (Select All, Invert, and Clear) to select the molecules to save. The dialog reports the total number of selected molecules and the total number of molecules in the list.

Mol2 Files SYBYL uses Mol2 files to store molecules resulting from most computations.

SYBYL-X 1.1

SYBYL Basics

39

Chapter 4. Open and Save Files of Molecules Save a Molecule File via the Menubar

Mol2 files are text files containing all information necessary to reconstruct the molecule. The format is based upon the convention of a keyword for each type of data needed to reconstruct the molecule, followed by a group of records. (See the Mol2 File Format chapter in the Toolkit Utilities Manual.) Colors are also saved. Additionally, any defined sets or features are saved to the Mol2 file. Default Names for Unnamed Molecules All molecules stored in a Mol2 file must have a name. This name is usually provided by the context of the operation or by the use via Edit > Molecule > Name. The command TAILOR SET MOL AUTO_NAME determines how to handle unnamed molecules: •

YES: unnamed molecules (single and MultiMol2) are named according

to the filename. •

NO: unnamed molecules are named “unnamed”.


40

•

Save a Molecule to a File on page 20 for an example exercise.

•


•


•

Read and Write PIR and FASTA Files in the Biopolymer manual.

•

Read and Write PDB Files in the Biopolymer manual.

•

TAILOR SET PDB in the Tailor manual.

•

SLN Files on page 42

•

SD/MDL Mol Files on page 42

SYBYL Basics

SYBYL-X 1.1

Chapter 4. Open and Save Files of Molecules Open/Save Mol2 Files via the Command Line

4.3 Open/Save Mol2 Files via the Command Line MOL direction [mol_area] [filename] direction

•

DIRECTORY—Report if specified file has Mol2 format, list

molecule(s) in the file, plus the number of atoms and bonds. IN—Read file containing a single molecule. MULT_IN—Read file containing several molecules, starting at the specified area and filling subsequent areas thereafter, until all molecules are read. Use DATABASE ADD to insert molecules into a new database. • MULT_OUT—Write file containing several molecules in several molecule areas. • OUT—Write file containing a single molecule in specified area. Molecule area to receive input data (IN, MULT_IN) or that contains molecule(s) to write to a file (OUT, MULT_OUT) or to the X clipboard (XCOPY, XPASTE). Contents of molecule areas are overwritten. File to read/write. When writing a file, if the filename already exists, it is overwritten. • •

mol_area

filename


Open Files via the Menubar on page 34

•


•


SYBYL-X 1.1

SYBYL Basics

41

Chapter 4. Open and Save Files of Molecules Open and Save in Other Formats

4.4 Open and Save in Other Formats 4.4.1 SLN Files Menubar:


) (specify the File Type as SLN)


) (specify the Format as SLN)

When a file that contains SLNs is opened, its contents are loaded into an MSS.

4.4.2 SD/MDL Mol Files The formats of an SD file and an MDL Mol file are published by Molecular Design Ltd. (MDL). SD files have a default extension of .sdf. MDL Mol files have a default extension of .mol. Read/Write SD/MDL Mol Files Menubar:

File > Import File ( ) (specify the File Type as MDLSDF) The contents of an MDL MOL file are loaded into a molecule area. The contents of an MDL SD file are loaded into an MSS. File > Export File ( SDF)

42

SYBYL Basics

) (specify the Format as MDL-

SYBYL-X 1.1

Chapter 4. Open and Save Files of Molecules Open and Save in Other Formats

Command Line:

MDLMOL IN|OUT|MULT_IN|MULT_OUT mol_area filename(s) • IN—Read an MDL Mol file. Assign correct atom and

•

• •

bond types (verify that they are correct before proceeding). Non-recognized atoms are assigned SYBYL’s type DU (dummy). Files with more than 999 atoms or bonds cannot be read. Note that normalization (aromatization and standardization) of the structures is done by default. To control this default behavior, use the command TAILOR SET TABLE MDL_NORM_AROM. OUT—Write a MDL Mol file. Use the molecule’s name as the file header name, and prompt for the header and comment line. SYBYL aromatic bonds are converted to alternating single and double bonds. SYBYL dummy atoms (DU) and lone pairs (LP) are removed from the atom list before file is written. MULT_IN—Read an SD file. MULT_OUT—Save multiple molecules to an SD file.

Note: To include hydrogens when saving to an SD or MDL Mol file, use TAILOR SET TABLE MDL_H_HANDLING to KEEP_ALL. Convert MDL Mol Files to Molecular Spreadsheet or UNITY Hitlist Menubar:

File > Import File ( ) (specify the File Type as MDLSDF). The contents of an MDL MOL file are loaded into a molecule area. The contents of an MDL SD file are loaded into a spreadsheet (MSS). File > Export File ( ) (specify the Format as SYBYL Table or UNITY Hitlist)

Command Line:

MDLMOL_CONVERT HITLIST|MSS input_file name_field output_file

• • •

SYBYL-X 1.1

input_file—Name of MDL Mol file to translate. name_field—Registration/Name field to look for in MDL Mol file (case sensitive). output_file—Name to assign to hitlist file or table generated.

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Chapter 4. Open and Save Files of Molecules Convert Between Molecular File Formats

4.5 Convert Between Molecular File Formats Convert molecular descriptions from one file format to another, performing some additional operations during the conversion process. For the expert: utilities described in the UNITY Manual •

dbtranslate: Translate between Molecule Formats

•

sln2img: Translate SLN or SMILES Files to PNG or GIF

UNITY > UNITY Tools > Translate Molecular Files or File > Translate Molecular Files

Input Options Enter SLN Mol Area File

44

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SLN for input structure. Molecule area containing structure. Type of input file: SLN, BCD (BinConf) (binary conformational data file), MDL-SDF, Original SMILES, Daylight SMILES, Conversational SMILES, SYBYL MOL2. Enter full path for file. (Press [...] to browse.) (Read about Binary Conformational Data Files in the UNITY Manual.)

SYBYL-X 1.1


Output Options SLN to Textport Mol Area File

Specify Options

SYBYL-X 1.1

Print SLN in the console. Display structure on screen. Select molecule area from the pull-down. Save results to file of specified type: SLN, BCD (BinConf) (binary conformational data file), MDL-SDF, Original SMILES, Daylight SMILES, Conversational SMILES, SYBYL MOL2, SLN Tabs (gives regID, a tab, then SLN, if the input is BCD, then the regIDs and number of conformations are provided in the output file). Enter full path for file. For BCD (BinConf), if the specified file exists, information will be appended to it (i.e., the contents will not be overwritten). Read about Binary Conformational Data Files in the UNITY Manual. Display the Translate Molecular File Options dialog for further translation choices.

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45


4.5.1 Specify Translation Options UNITY > UNITY Tools > Translate Molecular Files In the Translate Molecular File dialog, press Specify Options.

Generate Concord 3D Coordinates

Perceive Chirality at Carbons

46

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Use Concord to generate 3D coordinates. (Read about the use of Concord for this operation in the UNITY Manual.) Enter the number of structures to give to Concord per batch in the Batch Size field. Default is 500. Check for the chirality of carbon atoms based on 3D coordinates or, if coordinates are not present, bond stereo flags. Existing chirality attributes that perception determines are incorrect, will be removed. (Not recommended for 2D SD files.)

SYBYL-X 1.1


Perceive Chirality at N and P

Perceive Bond Stereochemistry

Include/Strip Property Data Standardize Structures

Standardization Rules File Output for SYBYL Compatibility

Fill Valences Aromatize Structures Convert to Kekule Validate Valences

Invalid Structures File

SYBYL-X 1.1

Set chirality for nitrogen and phosphorus atoms based on 3D coordinates or, if coordinates are not present, bond stereo flags. Existing chirality attributes that perception determines are incorrect, will be removed. (Not recommended for 2D SD files.) Set double bond stereo based on 3D coordinates or, if coordinates are not present, bond stereo flags. Use the environment variable PERCEIVE_RING_BONDS to control how stereo bond attributes are perceived in rings. Existing stereo attributes that perception determines are incorrect, will be removed. (Not recommended for 2D SD files.) Turn on to include property data. Check to enable standardization of structures by using rules defined in standard.defs (by default). (Read about Standardizing Structures in the UNITY Manual.) Specify a different file to use for standardization rules. Force output to be “SYBYL friendly.” Only six membered rings are aromatized, and charge separated nitro groups are converted to N(=O)=O. Two files residing in the UNITY tables directory (path set by TA_FILE_PATH) are used, mol2_arom.defs (special version aromaticity.defs), and mol2_standard.defs (special version of standard.defs). Fill valences of translated structure. Automatically perform aromatic normalization. Include aromatic bonds in MDL file. Only available when output file type is MDL-SDF. • Off—Prevent validation of structures. • Warning—Validate structures, but do not write invalid structures to a file. • Error—Validate structures and save invalid structures to designated file. File to hold invalid structures. Only valid if Validate is set to Error.

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Treatment of H’s in MDL-SD Files

MDL-SDF Field to use for Regid Expand Macro Atoms Unique Structures Split SLNs over Multiple Lines Fast Translation

Include/Strip Atom Chirality Include/Strip Stereo Bonds Attrs

Include/Strip 2D Coordinates Include/Strip 3D Coordinates Visual Report of Progress Report_Interval

Enable/Disable Debug Mode Write Errors to Log File

48

SYBYL Basics

How to handle hydrogens. Only valid when output type is SD File. • chiral_only—Keep hydrogens located on chiral atoms (default and MDL compatible). • remove_all—Remove all hydrogens. • keep_all—Keep all hydrogens. • carbon_remove—Remove all hydrogens located on carbons. Data label within a MDL SD file identifying registration name. Only valid when input file type is SD File. Replace macro atoms with constituent atoms, essentially exploding them. Canonicalize translated structure. Turn off to generate a single line SLN. Only valid when output file type is SLN. Use with Split SLNs over Multiple Lines to convert hitlist to/from multi-line SLN output. Only valid with SLN hitlists. Hitlist header information is preserved or created (if not present). Turn on to include chirality. When off, stereo bond attributes are stripped. Removal of stereo bond attributes occurs prior to stereo bond perception, when Perceive Bond Stereochemistry is on. Turn on to include 2D coordinates. Turn on to include 3D coordinates. Display progress information on host terminal. Number of structures to translate before reporting progress information. This option has no effect unless Visual Report of Progress is on. Turn on to display debugging messages. Name of log file to hold errors. Default is dbtranslate.log. Existing file is overwritten.

SYBYL-X 1.1

Chapter 4. Open and Save Files of Molecules View and Edit Text Files in SYBYL

4.6 View and Edit Text Files in SYBYL To edit text files using a text editor, select Edit > Text File from the SYBYL menubar. In the Edit File dialog, select the desired file. (The text editor can also be displayed using the SPL expression generator, %file_edit.) After you have specified the file to edit: 1. If you have the environment variable $EDITOR defined, it will preferentially use that editor to edit. (Note: If $EDITOR is defined as vi or vim, it will spawn an separate system shell.) 2. If $EDITOR is completely undefined, it will use the SPL editor. $EDITOR does not have to be defined at the system level, you could define it in SYBYL using setvar or in the sybyl.ini file (in your home directory): setvar EDITOR nedit

The SPL editor is described below.

Save Cancel

SYBYL-X 1.1

Save any changes made in the text field to the original file. Ignore any changes made in the text field and closes the text editor.

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49

Chapter 4. Open and Save Files of Molecules View and Edit Text Files in SYBYL

Save As Search Again Cut Copy Paste

50

SYBYL Basics

Specify a new location and/or file name in the Save Text File dialog. Search for the specified string entered in the displayed dialog. Locate the next occurrence of the search string. Remove highlighted text and place on the clipboard. Copy highlighted text to the clipboard. Paste text on the clipboard at the location of the cursor.

SYBYL-X 1.1

Chapter 5.

Understand Molecule and Display Areas •

What are Molecule and Display Areas? on page 52

•

Change the Default Molecule Area on page 54

•

Copy Between Molecule Areas on page 55

•

Merge Molecule Areas on page 56

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Chapter 5. Understand Molecule and Display Areas What are Molecule and Display Areas?

5.1 What are Molecule and Display Areas? A display area is where your molecule is displayed on the screen. SYBYL has four unique display areas: D1, D2, D3, and D4. Click the icon and select from the pull-down or click the icon to open the Display Options dialog and use the Screen options to change the placement on the screen. The figure below shows how molecules are displayed for each Screen option. Figure 1 Screen Modes for Display Options

A molecule area is a region of memory that holds a particular molecule. The total number of molecule areas does not have a fixed limit, because the number depends on your computer’s memory. Note that molecule areas have rules: •

M1 is always in display area D1.

•


•


•


If you use additional molecule areas, they recycle through the display areas:

52

•


•


•


•


SYBYL Basics

SYBYL-X 1.1

Chapter 5. Understand Molecule and Display Areas What are Molecule and Display Areas?

The figure below demonstrates this pattern. Figure 2 Display and Molecule Areas


Load Molecules on page 16 for an example exercise.

•

Change the Display on page 16 for an example exercise.

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SYBYL Basics

53

Chapter 5. Understand Molecule and Display Areas Change the Default Molecule Area

5.2 Change the Default Molecule Area The default molecule area is M1. Tip: If you are performing a number of operations on a structure in a different area (for example, M3), you can change the default to that area (M3), while working on that structure. Menubar: Command Line:

Options > Set > Default Molecule Area DEFAULT mol_area

The default molecule area is reported in the status bar at the bottom of the SYBYL window.

54

SYBYL Basics

SYBYL-X 1.1

Chapter 5. Understand Molecule and Display Areas Copy Between Molecule Areas

5.3 Copy Between Molecule Areas When items are copied between molecule areas, the source molecule area remains unchanged and the target area contains the copy. Copy the Contents of one Molecule Area to Another Menubar:

Edit > Copy Acts only on pre-selected atoms in a single molecule area.

Icon: Command Line:

on the Edit toolbar. COPY origin_atomexp target_area

•

•

origin_atomexp—Molecule area to duplicate (e.g., M1) or atom expression (e.g., M1(1,2,3,5,10) for atoms to duplicate. target_area—Molecule area to receive the duplicate structure/atoms.

Makes an exact copy of all selected contents (properties, colors, and associated background images) in one work area and places the copy in another area. The origin (source) molecule is not altered. The previous contents of the target area (if any) are moved to the recovery stack for that area. Extract Atoms and Associated Data Structures to a Different Molecule Area Menubar:

Edit > Extract Acts only on pre-selected atoms in a single molecule area.

Command Line:

EXTRACT atom_expr target_mol_area

Extracted atoms are removed from the origin area and replace the contents of the target area (by default the first empty molecule area). All local set definitions associated with the extracted atoms are copied to the new area. If atom_expr does not specify a work area, the default work area is used. If atomic charges are present in the target molecule before the extraction, the atoms still bear the same charges after the extraction. However, they are marked invalid, and will not be used on subsequent SYBYL operations. Validate these charges manually via the command: CHARGE mol_area VALIDATE YES.

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55

Chapter 5. Understand Molecule and Display Areas Merge Molecule Areas

5.4 Merge Molecule Areas Merging combines a copy of selected atoms in the source molecule area with the contents of the target area. Unique Atom: The following scenarios define a unique atom: •

If the coordinates and the atom types in both the source and the target area are different, an atom is considered to be unique.

•

If the coordinates in the source and the target area are the same, but the atom types are different, an atom is considered to be unique.

•

If the atom types in the source and the target are the same, but the coordinates are different, an atom is considered to be unique.

You can set the distance within which two atoms are considered identical and whether to keep only unique atoms with TAILOR SET MERGE. Non-unique Atom: An atom in the source area with the same atom type and coordinates as an atom in the target area. See Merging Non-Unique Atoms on page 58 Additional Information: •

Combine (Join) Two Molecules on page 135

•

TAILOR SET MERGE to alter the characteristics of merging.

5.4.1 Merge Atoms and Associated Data Structures Tip: If molecules have been rotated and/or translated, use View > Transformations > Freeze to transform the coordinates before merging. Edit > Merge Acts only on pre-selected atoms in a single molecule area.

Menubar:

Command Line:

MERGE atom_expr target_area

If atom_expr does not specify a work area, the default work area is used. Check the output displayed in the console for messages about the merge. Special conditions apply when merging non-unique atoms and features. When you merge atoms and associated data structures, most of the associated data structures are kept in the merge. These include: •

ATOM •

56

Atom type

SYBYL Basics

SYBYL-X 1.1


•

•

•

Atom alternate type (Amber/Kollman/MMFF94 types)

•

Atom name

•

Charges

•

Atom ID is not kept.

BOND •

Bond type

•

Bond ID is not kept.

SUBSTRUCTURE •

Substructure type

•

Substructure name

•

Substructure ID is not kept.

•

CENTER_OF_MASS—If a CENTER_OF_MASS in the source area has the same name as one in the target area, the one in the source area is not merged.

•

CENTROID—If a CENTROID in the source area has the same name as one in the target area, the one in the source area is not merged.

•

Constraints—If an atom associated with a constraint is not merged, the constraint is also not merged. (Refer to the Constraint chapter in the Force Field Manual.) •

FFCON_ANGLE

•

FFCON_DIST

•

FFCON_MULTI

•

FFCON_RANGE

•

FFCON_TORSION

•

PLANE—If a PLANE in the source area has the same name as one in the target area, the one in the source area is not merged. Since a plane always has an associated NORMAL, if that NORMAL is not merged, the PLANE is not merged.

•

NORMAL—If a NORMAL in the source area has the same name as one in the target area, the one in the source area is not merged.

•

SET—Any set in the source area with the same name as the set in the target area will be combined into a single set when merged.

Note: If CENTER_OF_MASS, CENTROID, PLANE, or NORMAL is defined on a molecule, SYBYL creates dummy atoms representing features (e.g. center of a centroid). These dummy atoms need to be selected for merging or the whole feature information is not merged.

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SYBYL Basics

57


The associated data structures that are not merged include: •

ANCHOR_ATOM

•

EXTENSION_POINT

•

FF_PBC

•

RING_CLOSURE

•

ROTATABLE_BOND

•

U_FEAT

•

UNITY_ATOM_ATTR

•

UNITY_BOND_ATTR

5.4.2 Merging Non-Unique Atoms Normally there is nothing to merge if two atoms are “non-unique”. There are some cases however, where they may be merged. Non-unique atoms from the source area may be merged into the target area when both of the following conditions have been met: •

The non-unique atom in the source molecule area has a unique atom attached to it.

AND •

In the target molecule area there is no open valence on the atom corresponding to the non-unique atom in the source molecule area.

The unique atom carries with it the non-unique atom to preserve the bonding information. Example: Merging Non-Unique Atoms Read in a methane molecule into M1 and into M2. Then change one of the hydrogens in the M1 methane molecule to bromine.

¾ ¾ ¾ ¾ ¾ ¾ 58

File > Get Fragment Select METHANE and press OK. File > Get Fragment Select METHANE and press OK. Use

on the Display toolbar to set the screen mode to Half.

Edit > Atom > Modify

SYBYL Basics

SYBYL-X 1.1


¾ ¾

In the Option dialog, select TYPE and press OK. In the Atom Expression dialog, click one of the hydrogen check boxes and press OK.

¾

In the Option dialog, select Br and press OK.

Relative to M2, the carbon and hydrogens in M1 are non-unique atoms, while the bromine is a unique atom. Merging M1 into M2 will bring the non-unique carbon and the unique bromine from the source area to the target area (M2).

¾ ¾ ¾

Double-click any atom in M1 to select the whole molecule. Edit > Merge In the Molecule Area dialog, select M2:methane and press OK.

M2 now contains 7 atoms. To verify the contents of M2:

¾ ¾

Options > List > Atoms In the Atom Expression dialog, select M2 from the pull-down at the top of the dialog.

¾ ¾ ¾

Press

.

Press OK. In the Option dialog, select BRIEF and press OK.

The console reports something similar to the following: Molecule area M2 Atoms Molecule Name: methane Number of defined atoms: id

7

name substructure type x ---------------- ---1 C1 METHANE C.3 0.0000 2 H1 METHANE H -0.2694 3 H2 METHANE H 0.9250 4 H3 METHANE H 0.1572 5 H4 METHANE H -0.8128 6 BR1 METHANE Br -0.4747 7 METHAN+ METHANE C.3 0.0000 Number of atoms selected for listing: 7

¾

When finished, use the

¾

Edit > Delete Everything

SYBYL-X 1.1

y 0.0000 -0.7900 0.4950 -0.4444 0.7394 -1.3919 0.0000

z charge -----0.0000 0.000 0.7164 0.000 0.3308 0.000 -0.9939 0.000 -0.0533 0.000 1.2622 0.000 0.0000 0.000

icon to reset the screen mode to Full.

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59


Chapter 6.

Select Atoms, Bonds, or Substructures •

Selecting With the Mouse on page 62

•

The Selection Menu and Icons on page 63

•

General Description of the Expression Dialogs on page 67

•

Tutorials: •

How to Use the Atom Expression Dialog on page 75

•

How to Use the Bond Expression dialog on page 82

•

How to Use the Substructure Expression Dialog on page 85

Selection of atoms, bonds, or substructures (such as residues in a protein) can be as simple as clicking on the desired objects in the SYBYL display area. More complex selection may be based on a particular type or a defined set, and may use Boolean operations. Many menubar and toolbar operations in SYBYL will operate on the current selection in the display area. For example, selecting several atoms in the display area and then clicking on the Display toolbar immediately changes the rendering of the selected atoms (and connecting bonds) to be capped sticks. Additional Information: •

Formats for Specifying Objects on page 202.

•

Create Complex Expressions on page 211.

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Chapter 6. Select Atoms, Bonds, or Substructures Selecting With the Mouse

6.1 Selecting With the Mouse One-click selection: •

Click on an atom to select it. If the atom is spacefilled you must click in the center of the sphere to select the atom.

•

Click on a surface or ribbon to select it.

Select a residue or substructure: •

Double-click on any atom in a residue to select the entire substructure.

Select an entire molecule •

Triple-click on any atom to select everything in the molecule area. In the context of a biopolymer complex, this means the biopolymer itself as well as any ligand, cofactor, metal and waters in the same molecule area.

Select all atoms in a rectangular area •

Ctrl+Alt while dragging the mouse to select all atoms in the area outlined by a rectangle.

Toggle the selection state of an object •

Ctrl+click an atom or surface to add it to or remove it from the current selection.

•

Ctrl+double-click any atom to toggle the selection station of its substructure.

•

Ctrl+triple-click any atom to toggle the selection state of the entire molecule area.

Clear all selection

62

•

Click anywhere on the SYBYL backdrop.

•

Click

SYBYL Basics

.

SYBYL-X 1.1

Chapter 6. Select Atoms, Bonds, or Substructures The Selection Menu and Icons

6.2 The Selection Menu and Icons On the SYBYL menubar: Selection

Usage Note: Atoms that are invisible cannot be selected and, therefore, cannot be acted upon unless the operation affects the entire molecule area.

6.2.1 Expand the Selection This functionality is enabled only if at least one atom has been selected. Access: •

Menubar: Selection > Expand

•

Icon:


To Anything Connected

To Substructure

To Chain

SYBYL-X 1.1

The selection expands to include all atoms contiguously connected to the pre-selected atom(s). For example, in a protein/ligand complex with a ligand atom selected, expansion selects all atoms in that ligand and none of the protein atoms nor any atoms in additional structures such as water, metal or other ligands. The selection expands to include all atoms in the substructure(s) that contain pre-selected atom(s). For example, in a protein with atoms selected in two residues, expansion selects all atoms in those residues. The selection expands to include all atoms in the protein chain(s) that contain pre-selected atom(s).

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63


To Biopolymer

To Structure Within a Radius

The selection expands to include all biopolymer atoms in the molecule area(s) that contain pre-selected atom(s). Biopolymer atoms are those that fall in the Residues listing of the Atom Expression dialog. Examples given a solvated protein/ligand complex: • If one protein atom is selected, expansion selects the entire protein, but not ligand, solvent, or any other non-protein atoms. • However, if the waters are selected, expansion adds all protein residues to the selection. The same apply to a pre-selected ligand or cofactor. The selection expands to include all atoms in all the molecule areas that contain pre-selected atoms. The selection expands to include atoms in all molecule areas that are within the specified radius of pre-selected atoms. • For small molecules the expansion selects atoms within the specified radius. • For biopolymers the expansion includes all substructures that have any atom within the specified radius.

6.2.2 Invert the Selection This functionality is enabled only if at least one atom has been selected. Access: •

Menubar: Selection > Invert

•

Icon:


Within Selected Molecule Areas Over All Molecule Areas

Of Molecule Areas

64

SYBYL Basics

The atom selection is inverted, but only within the molecule area(s) that contain selected atom(s). The atom selection is inverted over all molecule areas. For example, with two molecule areas occupied and only a single atom selected, inverting the selection over all areas selects all atoms in both molecule areas and deselects the atom that was originally selected. Inversion of the selection depends on the original selection: • For molecule areas that contain selected atom(s), all atoms will be deselected. • For molecule areas that do not contain selected atom(s), all atoms will be selected.

SYBYL-X 1.1


6.2.3 Clear the Selection Clear the selection from all objects. This feature is available only if at least one object has been selected. Access: •

Mouse: click the left button in an unoccupied area of the SYBYL backdrop.

•

Menubar: Selection > Clear

•

Icon:

•

Keyboard Shortcut: Ctrl+D


6.2.4 Select All or Specified Atoms All Atoms Select all atoms in all molecule areas. Access: •

Menubar: Selection > All Atoms

•

Keyboard Shortcut: Ctrl+A

Some Atoms in a Single Molecule Area Launch the Atom Expression dialog. If multiple molecule areas are occupied you will be prompted to select the one of interest. Only the atoms selected in the dialog will be selected when the dialog is closed via its OK button. Access: •

Menubar: Selection > Select Atoms

•

Icon:


All Atoms in Specified Molecule Area(s) Select all atoms in the molecule areas selected via the Molecule Expression dialog. If only one molecule area is occupied all atoms within it are selected automatically. Access: •

SYBYL-X 1.1

Menubar: Selection > Select Molecules

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65


6.2.5 Select Atoms in Biopolymers The following options of the Selection menu make use of sets and the macromol dictionary to select atoms in all molecule areas that contain molecules of type “biopolymer” (protein, DNA, RNA, carbohydrate). Biopolymer Backbone Sidechain Ligand

Water Metal

Use the {BIOPOLYMER} built-in set to select all amino acids and nucleic acids. Use the {BACKBONE} built-in set to select all backbone atoms in all molecule areas. Use the {SIDECHAIN} built-in set to select all sidechain atoms in all molecule areas. Use the {BIOPOLYMER(LIGAND} set to identify all ligand atoms. Note that ligand atoms in a molecule area that does not contain any residues may also be identified by show and hide operations. This is because copying or extracting a ligand from, for example, a protein/ligand complex into a new molecule area assigns the type “biopolymer” to the new molecule. Use the {WATER} set to select all water atoms in all molecule areas. Use the {METAL} built-in set to select all metal atoms in all molecule areas.

Usage Note: Atoms that are invisible cannot be selected and, therefore, cannot be acted upon unless the operation affects the entire molecule area. For example, if only the protein and water atoms within a 5 Å radius of a ligand are currently visible, the Selection > Water operation will select only the visible waters, not all of them. A subsequent deletion of the selected atoms will delete only those few visible waters, leaving all others invisible, but still present.

6.2.6 Select Hydrogens The following options of the Selection menu use hydrogens as the basis for selecting atoms in all molecule areas. Non-Hydrogens Hydrogens Polar Hydrogens Non-Polar Hydrogens

66

SYBYL Basics

Select all non-hydrogens in all molecule areas. Select all hydrogens in all molecule areas. Use the {POSSIBLE_HBOND} built-in set to select hydrogens in all molecule areas. Select all non-polar hydrogens in all molecule areas.

SYBYL-X 1.1

Chapter 6. Select Atoms, Bonds, or Substructures General Description of the Expression Dialogs

6.3 General Description of the Expression Dialogs Access: •

Menubar: Selection > Select Atoms

•

Icon:


SYBYL’s Expression dialogs are designed to allow as much flexibility as possible.

6.3.1 The Main Expression Dialog As selections are made by clicking on objects in SYBYL’s display area or using the various buttons, an expression is formed. Activating the Show Atom Expression check box will expand the dialog so that the expression is visible.

The expression itself shows the molecule area and current “formula” that the program will use to select the objects for the action being performed. As you become familiar with expressions, you may enter them directly in the field. Note that no atoms will be highlighted until you press Apply.

The Expression dialog is presented under several different titles depending on context: Atom Expression, Bond Expression, Substructure Expression, Sequence Expression. Although the various Expression dialogs are very similar in layout, there are differences. These differences are noted in the description below.

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Molecule Area

Hierarchy

Selected

68

SYBYL Basics

In the pull-down select the molecule area in which the selection will be made. Usage Notes: • Picking from the screen is enabled only in this designated molecule area. • When the dialog is invoked via the icon (Selection > Select Atoms), the molecule area is set automatically to that of a pre-selected atom or, if nothing had been selected, to the current default molecule area as reported at the bottom of the SYBYL window (set via Options > Set > Default Molecule Area). Contains a hierarchical representation of the structural contents in the specified molecule area. • When applicable, the different levels can be expanded and collapsed by clicking the “+” and “-”, respectively. • Click an item in the hierarchy to select it (a check mark appears in the check box). Atoms that are hidden cannot be selected. • When an item with subitems is selected, all its subitems are also selected. • When one or more subitems are selected, the check box of the main item will contain a grey check mark to indicate a partial selection. • Right-click menus are available with options for inverting the current selection. For proteins, the menu options allow for various degrees of inversion (e.g., invert the selection within the substructure, within the chain, or the entire protein). • If a protein has missing residues within a chain, you will see multiple entries for that chain, one for each continuous chain of residues. The residue number range for each portion of the chain is shown in parentheses. Buttons to assist in selecting items in the hierarchy: select all, invert selection, clear selection. Displays the number of objects that are selected in the currently active molecule area.

SYBYL-X 1.1


Pick by

Show Expression

Create Set

SYBYL-X 1.1

In addition to selecting items in the hierarchy, the following options allow you to define selections based on different categories of items (e.g., a particular residue type, a predefined set, anything within a radius of an atom, etc). Boolean operations are available for combining the selections with any hierarchical selections. • Atoms—Available only in the Bond Expression dialog. Displays the Atom Expression dialog for selecting bonds based on an atom expression. • Substructures—Available in the Atom Expression and Bond Expression dialogs when a protein is displayed. Displays the Substructure Expression dialog for selecting atoms based on residue, water, or other defined substructure. • Sets—Displays the Sets Selection dialog for basing selection on defined sets, a radius, chirality, and/or conformation. The options available depend on the Expression dialog from which the Sets Selection dialog is launched. • Types—Displays the Types dialog for basing selection on particular types of atoms, bonds, or residues (depending on the Expression dialog from which the Sets Selection dialog is launched). Activate to expand the dialog to display a field containing the selection expression. Deactivate to collapse the dialog by hiding the expression field. You type a new or modify the existing expression in this field. If you do, press Apply. See SYBYL Objects and Their Expressions on page 197. Defines a new set containing the selected items. Specify a name for the set. This new set is added to the list of predefined sets in the Sets dialog. (Note: The new set is temporary unless you save the molecule. Otherwise, it is lost once the molecule is deleted from the display.)

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69


Boolean Action Buttons

The Boolean operators can be used to combine two groups of selected items. These buttons appear only when the Atom Expression or Substructure Expression dialogs are accessed by clicking Pick by Atoms or Substructures in another Expression dialog where selections have been made. • Intersect—Find the common items between the selection identified in this dialog and the previous selection. The remaining highlighted items are those found in both groups of selected items. • Remove—Subtract the items selected in this dialog from the previous selection. The remaining highlighted items are those found in the first group of selected items, but not the second. • Add—Add to the previous selection. The remaining highlighted items are in either of the two groups of selected items.

Usage Note: Atoms that are invisible cannot be selected and, therefore, cannot be acted upon unless the operation affects the entire molecule area. For example, if only the protein and water atoms within a 5 Å radius of a ligand are currently visible, the Selection > Water operation will select only the visible waters, not all of them.A subsequent deletion of the selected atoms will delete only those few visible waters, leaving all others invisible, but still present. Additional Information:

70

•

Formats for Specifying Objects on page 202.

•

How to Specify an Atom Expression on page 203

•

How to Specify a Bond Expression on page 205

•

Monomer Sequence Specification on page 208

•


SYBYL Basics

SYBYL-X 1.1


6.3.2 Atom, Bond, Residue Types The contents of the Types dialog depends on the Expression dialog from which it was launched. In an Expression dialog, press Types. Atom Types

Type List

Sort Alphabetically

SYBYL-X 1.1

Residue Types

Lists available types for the atoms, bonds, or residues. • The Atom Types dialog displays a hierarchy of atom names and types. It functions the same way as the Expression dialog hierarchy in terms of making selections and expanding/collapsing lists. • When bonds are being selected based on atom types, all bonds connected to specified atoms are highlighted. • Bond types include: 1 (single), 2 (double), 3 (triple), am (amide), ar (aromatic), du (dummy), un (unknown, cannot determine from the parameter tables), nc (non-chemical). • The Bond Types and Residue Types dialogs are simple lists of types. Click multiple items to select them. Click again to remove from the selection. Sorts the list of residues alphabetically when turned activated. Available only in the Residue Types dialog.

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71



The Boolean operators can be used to combine two groups of selected items. • Intersect—Find the common items between the selection identified in this dialog and the previous selection. The remaining highlighted items are those found in both groups of selected items. Available only when a selection has been made in the Expression dialog from which this dialog was launched. • Remove—Subtract the items selected in this dialog from the previous selection. The remaining highlighted items are those found in the first group of selected items, but not the second. Available only when a selection has been made in the Expression dialog from which this dialog was launched. • Add—Add to the previous selection. The highlighted items are in either of the two groups of selected items.


General Description of the Expression Dialogs

6.3.3 Sets for Atom, Bond, and Substructure Selection The contents of the Sets Selection dialog depends on the Expression dialog from which it was launched. Although the various Sets Selection dialogs are very similar to each other in layout, there are differences. In the dialog description below, these differences are noted. In an Expression dialog, press Sets. Atom Sets

72

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Substructure Sets

SYBYL-X 1.1


Chirality Sphere

Built-In Sets

Sets

Conformations


Selects a set of atoms that have a particular chirality. Available only in the Sets for Atom Selection dialog. Selects a set of atoms that fall within the specified radius of currently selected atoms. Available in the Sets for Atom Selection and Sets for Substructure Selection dialogs. Selects atoms that belong to a particular built-in set. (Note that the Rings option will identify internal and external ring systems.) See Built-in Sets on page 223 for definitions of these sets. Available in the Sets for Atom Selection and Sets for Bond Selection dialogs. Selects atoms that are part of a global or local set. Use the Ctrl key to select multiple items in the list. See Local Sets on page 220 and Global Sets on page 217 for more information. Selects substructures that form a particular conformational state in a protein. This list contains residue conformational states as defined in the macromol dictionary. See the Dictionary Files description in the Biopolymer Manual. Available only in the Sets for Substructure Selection dialog. The Boolean operators can be used to combine two groups of selected items. • Add—Add to the previous selection. The remaining highlighted items are in either of the two groups of selected items. • Intersect—Find the common items between the selection identified in this dialog and the previous selection. The remaining highlighted items are those found in both groups of selected items. Available only when a selection has been made in the Expression dialog from which this dialog was launched. • Remove—Subtract the items selected in this dialog from the previous selection. The remaining highlighted items are those found in the first group of selected items, but not the second. Available only when a selection has been made in the Expression dialog from which this dialog was launched.


SYBYL-X 1.1

General Description of the Expression Dialogs

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73


6.3.4 Molecule Expression The Molecule Expression dialog is used when the context calls for identifying a molecule(s) on which to operate.

Molecule List

List of currently displayed molecules. Buttons to assist in selecting items in the list: select all, invert selection, clear selection.


74

General Description of the Expression Dialogs on page 67.

SYBYL Basics

SYBYL-X 1.1

Chapter 6. Select Atoms, Bonds, or Substructures How to Use the Atom Expression Dialog

6.4 How to Use the Atom Expression Dialog The purpose of this tutorial is to explore the functionality offered by the Atom Expression dialog. The topics specifically covered include: •

•

General Tools for Atom Selection on page 75 •

Simple Atom Selection on page 76

•

The Atom Expression on page 76

•

Select Atoms by Type on page 78

•

Select Atoms via Defined Sets on page 78

Atom Selection Tools for Proteins on page 80

A Matter of Time: This tutorial requires 5 minutes of personal time. Additional Information: •


•


•


6.4.1 General Tools for Atom Selection Setup It is always a good idea to clear the screen and reset the display before starting.

¾ ¾

> Delete Everything Click

on the View toolbar to reset all rotations and translations.

Load dicloxacillin.

¾ ¾ ¾ ¾ ¾

SYBYL-X 1.1


)

In the Open File dialog set the Files of Type to SYBYL Mol2. In the list of Bookmarks select [$TA_DEMO]. In the Directory Navigation list select example.mdb. In the Selection list select dicloxacillin.mol2 then click OK.

SYBYL Basics

75


Simple Atom Selection Invoke the Atom Expression dialog.

¾

Selection > Select Atoms or press

¾

Ctrl+click a few atoms in the molecule.

.

The selected atoms are highlighted on the screen. In the dialog the check boxes for the selected atom are flagged, and a line below the list reports the number of currently selected atoms.

¾

In the Atom Expression dialog, press

(Select All).

All 49 atoms are selected in the dialog and highlighted on the screen.

¾

Press

(Clear Selection).

0 atoms are selected.

¾

Select any three atoms in the dialog or Ctrl-click to select them in the molecule.

¾

Ctrl-click one of the three atoms a second time. That atom is no longer selected or highlighted.

¾

Press the

icon to invert the selection.

47 atoms are selected.

¾

Press

to clear the selection.

Usage Notes: •

If multiple molecule areas are occupied, picking from the screen is enabled only in the molecule area designated at the top of the dialog.

•

When the dialog is invoked via the icon (Selection > Select Atoms), the molecule area is set automatically to that of a pre-selected atom or, if nothing had been selected, to the current default molecule area as reported at the bottom of the SYBYL window (set via Options > Set > Default Molecule Area).

The Atom Expression Selected atoms are stored in an atom expression. This information is accessible at the bottom of the dialog.

¾

76

At the bottom of the Atom Expression dialog activate the Show Atom Expression check box.

SYBYL Basics

SYBYL-X 1.1


¾

Click one atom in the molecule to select it. The Atom Expression field echoes the atom’s ID number.

¾

Ctrl-click to select a few more atoms. Each atom’s corresponding ID number is echoed within the parentheses in the expression.

¾

Press


The expression acknowledges that nothing is selected: M1(empty).

¾

Press

to select all atoms.

An asterisk (*) appears between the parentheses. This represents all atoms in the molecule. You can also type atom ID numbers directly into the field.

¾

In the expression field delete * then type 4,5,6,7 within the parentheses.

¾

Press Apply. Nothing happens to the molecule until you press Apply. Four atoms are highlighted.

SYBYL-X 1.1

SYBYL Basics

77


¾ ¾

Press the

icon.

Deactivate the Show Atom Expression check box.

Refer to SYBYL Objects and Their Expressions on page 197 for a complete description. Select Atoms by Type

¾ ¾ ¾

At the bottom of the Atom Expression dialog, click Types to display a list of atom types. Activate the O check box. Click the + to expand the O category. All oxygen atom types defined within SYBYL are selected in the list.

¾

Press Add to return to the Atom Expression dialog. The five oxygens are highlighted in the molecule and in the dialog.

So far, you have added atoms to your selection. Now try subtracting the carbonyl oxygens to keep only the other two.

¾ ¾ ¾ ¾

Press Types. In the Atom Types dialog, click the + to expand the O category again. Activate the check box for O.2 in the list. Press Remove. Only two oxygens remain selected.

¾

Press


Select Atoms via Defined Sets SYBYL includes a wide variety of rule-based sets that can be applied to select atoms. Examples of these are Aromatic, H-bonds, Backbone, Sidechain, Rings, etc. See Built-in Sets on page 223. 1. Select all atoms that are aromatic.

¾ ¾

78

In the Atom Expression dialog, click Sets to open the Sets for Atom Selection dialog. Activate the Aromatic check box and press Add.

SYBYL Basics

SYBYL-X 1.1


All carbons in the phenyl ring are selected.

¾

Activate the Show Atom Expression check box. The field below the list shows the expression that is used to locate all (*) aromatic atoms: {AROMATIC(*)}. Set names must always be surrounded by braces.

¾

Press


2. Locate all rings within this molecule.

¾ ¾

Press Sets. In the Sets for Atom Selection dialog, activate the Rings check box and press Add. Four rings are identified and the Atom Expression field has a defined argument to locate all atoms within a ring.

3. Find all nitrogen atoms in rings. You have already selected Rings in the Atom Types dialog, now select another criteria.

¾ ¾ ¾

Press Types. In the Atom Types dialog, activate the N check box. Press Intersect. The Intersect operator can be thought of as a true “AND” filter in that both conditions must be met. Two nitrogen atoms are now selected. This is because only two of the three nitrogens are also part of a ring.

¾

In the Atom Expression dialog, deactivate the Show Atom Expression check box.

4. This concludes the exercise.

¾ ¾

SYBYL-X 1.1

Press


Press Cancel to close the Atom Expression dialog.

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79


6.4.2 Atom Selection Tools for Proteins Most of the time selections in protein involve residues. See the How to Use the Substructure Expression Dialog on page 85 for examples. There are times, however, when the selection must consist of atoms, not full residues. The following exercise is one such example. 1. Clear the screen.

¾

> Delete Everything

2. Load crambin from a file in SYBYL’s demo directory.

¾ ¾ ¾ ¾


)

In the Open File dialog set the Files of Type to PDB. In the list of Bookmarks select [$TA_DEMO]. In the Selection list select 1crn.pdb then click OK.

Select Atoms via Defined Sets 3. Invoke the Atom Expression dialog.

¾

Selection > Select Atoms or press

.

4. Invoke an operation that requires an atom selection.

¾

In the Atom Expression dialog click on the PHE13 check box.

The 11 atoms in PHE13 are highlighted. 5. Find all atoms that are within a 4 Å sphere of any PHE13 atom.

¾ ¾ ¾

Press Sets. In the Sets for Atom Selection dialog activate Sphere and type 4 in the field. Press Add.

All atoms within the specified radius are highlighted in the molecule. Notice that the selection does not include complete residues.

80

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6. In the dialog notice that some of the check boxes are colored to indicate partial selection within the corresponding residues.

¾

In the dialog expand the hierarchy for any of the partially selected residues to see the atom(s) selected within.

7. Reduce the current atom selection to sidechain atoms only. You will use a builtin set defined for that purpose.

¾ ¾ ¾

Press Sets. In the Sets for Atom Selection dialog activate the Sidechain built-in set. Press Intersect.

19 atoms are selected: all sidechain atoms within a 4 Å sphere around any PHE13 atom.

¾

If you are curious about the expression used to identify these atoms, activate the Show Atom Expression check box.

8. Color the selected atoms. You can do this via the toolbar while the dialog is open.

¾

Use the icon’s arrow to select and apply your favorite contrasting color.

9. The SYBYL menubar is disabled while the Atom Expression dialog is open.

¾

Press OK to exit the Atom Expression dialog with the current selection.

This concludes the exercise.

SYBYL-X 1.1

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81

Chapter 6. Select Atoms, Bonds, or Substructures How to Use the Bond Expression dialog

6.5 How to Use the Bond Expression dialog A Matter of Time: This tutorial requires a couple of minutes of personal time. Additional Information: •


•


6.5.1 Setup 1. Load dicloxacillin from a file in SYBYL’s demo directory.

¾ ¾ ¾ ¾ ¾


)

In the Open File dialog set the Files of Type to SYBYL Mol2. In the list of Bookmarks select [$TA_DEMO]. In the list of Directory Navigation select example.mdb. In the Selection list select dicloxacillin.mol2 then click OK.

2. Invoke a SYBYL feature that affects bonds.

¾ ¾

Edit > Bond > Modify Type Select TYPE and press OK.

SYBYL opens the Bond Expression dialog.

¾

If multiple molecules are currently on the screen, you must designate the molecule area of interest at the top of the dialog.

6.5.2 Select a Bond on the Screen

¾

Hold the Ctrl key and click two atoms that are bonded to each other.

The corresponding bond is highlighted in the dialog. An information line below the hierarchy reports that 1 bond is currently selected.

¾

To clear the selection click anywhere on the SYBYL backdrop or press the

82

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icon in the dialog.

SYBYL-X 1.1


6.5.3 Select all Bonds Connected to an Atom

¾

In the Bond Expression dialog, press Atoms.

The Atom Expression dialog is posted and automatically set to the same molecule area.

¾

Click on the nitrogen in the fused (β-lactam) ring system then press Add.

The three bonds between the nitrogen and its highlighted neighbors are selected in the dialog.

¾

Press the

icon to clear the selection.

6.5.4 Select Bonds by Type

¾

In the Bond Expression dialog, press Types.

All bond types are presented in the Bond Types dialog.

¾

Press ar then Add.

All aromatic carbons are highlighted, and the dialog reports that 6 bonds are currently selected.

¾

Press the

icon to clear the selection.

6.5.5 Select Bonds via Defined Sets

¾

In the Bond Expression dialog, press Sets.

The Sets for Bond Selection dialog presents named definitions that can be used to identify bonds. •

A few built in sets can be applied to bonds. See Built-in Sets on page 223.

•

Special purpose sets are defined in the macromol dictionary. See Global Sets in the Biopolymer Dictionary on page 218.

Most defined sets pertain to biopolymers. However, one of them can be used as an example for this tutorial: Rings.

¾

In the Built-in Sets section, activate Rings then press Add.

On the screen all ring atoms are highlighted. In the dialog the 19 bonds between these atoms are selected.

SYBYL-X 1.1

SYBYL Basics

83


¾

Press the

icon.

This concludes the exercise about the Bond Expression dialog.

¾

84

Press Cancel to close the dialog.

SYBYL Basics

SYBYL-X 1.1

Chapter 6. Select Atoms, Bonds, or Substructures How to Use the Substructure Expression Dialog

6.6 How to Use the Substructure Expression Dialog Selecting a substructure can be done easily by double-clicking any of its atoms. The purpose of this tutorial is to explore the functionality offered by the dialog. A Matter of Time: This tutorial requires a couple of minutes of personal time. Additional Information: •


•


6.6.1 Setup 1. Load crambin from a file in SYBYL’s demo directory.

¾ ¾ ¾ ¾


)

In the Open File dialog set the Files of Type to PDB. In the list of Bookmarks select [$TA_DEMO]. In the Selection list select 1crn.pdb then click OK.

2. Label the residues.

¾

Use on the View toolbar to label the substructures (Molecules > Substructure).

3. Invoke a SYBYL feature that affects substructures.

¾

Biopolymer > Composition > Mutate Monomers

SYBYL opens the Sequence Expression dialog.

¾

If multiple molecules are currently on the screen, you must designate the molecule area of interest at the top of the dialog.

6.6.2 Select Residues on the Screen

¾ ¾

SYBYL-X 1.1

Click on any atom of a single residue. The most reliable way to select a particular residue is to select its alpha carbon, the atom bearing the residue’s substructure label. To add to the selection, hold the Ctrl key while you click on another residue.

SYBYL Basics

85


Below the hierarchy in the dialog a line reports the number of substructures currently selected.

¾

To clear the selection click anywhere on the SYBYL backdrop or press the

icon in the dialog.

6.6.3 Select Residues by Name in the Dialog

¾

In the Sequence Expression dialog, click and drag to select VAL8 through ASN12.

All atoms in the selected residues are highlighted in the display area. Below the hierarchy in the dialog a line reports that 5 substructures are currently selected.

¾

Press the

icon (Clear Selection).

6.6.4 Select Residues by Type

¾

In the Sequence Expression dialog, click Types to open the Residue Types dialog.

The Residue Types dialog lists all possible monomer types available in the dictionary. The standard amino acids are in the leftmost column. You can also Sort Alphabetically to facilitate selection.

¾

In the Residue Types dialog, select CYS in the list and press Add. The six CYS residues are highlighted with the green selection markers.

¾

Press the

icon (Clear Selection).

6.6.5 Select Residues via Defined Sets

¾

In the Sequence Expression dialog, press Sets to open the Sets for Substructure Selection dialog.

All sets in this dialog are substructure sets, which means that they apply to entire residues. The list of sets is compiled from two sources: •

Special purpose sets whose definitions are stored in the macromol dictionary. See Global Sets in the Biopolymer Dictionary on page 218.

•

Sets that were created automatically by SYBYL upon reading the PDB file. See sets created upon reading a PDB file (in the Biopolymer Manual).

Selection based on conformational states, as defined in the dictionary, can also be made in this dialog.

86

SYBYL Basics

SYBYL-X 1.1


¾

Select HELIX_H1_PDB from the Sets list and press Add.

All atoms in residues in one of the two helices are highlighted with the green selection markers. This concludes the exercise about the Substructure Expression dialog.

¾

SYBYL-X 1.1

Press Cancel to close the dialog.

SYBYL Basics

87


Chapter 7.

Clear and Reset the SYBYL Display •

•

SYBYL-X 1.1

Clear the Screen and Delete Objects on page 90 •

Clear the Screen on page 90

•

Delete Selected Molecules, Atoms and Backgrounds on page 90 •

Delete Molecules on page 90

•

Delete Atoms on page 91

•

Delete Backgrounds on page 91

•

Delete Whatever is Selected on page 92

Reset Scaling, Translation, and Rotation on page 93

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Chapter 7. Clear and Reset the SYBYL Display Clear the Screen and Delete Objects

7.1 Clear the Screen and Delete Objects The

icon on the Edit toolbar consists of two buttons:

•

Click the X to delete whatever is currently selected.

•

Use the pull-down arrow to specify what will be deleted.

7.1.1 Clear the Screen Delete absolutely everything in the SYBYL window. Menubar: Icon:

Command Line:

Edit > Delete Everything Click the icon’s arrow and select Delete Everything. ZAP * to remove all molecules and associated background images followed by BACKGROUND DELETE * to remove all remaining independent background images.

All molecules and all graphics images, known as backgrounds, are removed from the SYBYL window.

7.1.2 Delete Selected Molecules, Atoms and Backgrounds For information on how to select objects refer to: •


•


•


Delete Molecules Clear the molecule areas containing the selected molecules. This functionality is enabled on the menubar and icon only if at least one atom has been selected. Menubar: Icon:

Select atom(s) in one or more molecules then Edit > Delete > Selected Molecules Select atom(s) in one or more molecules then Click the ecules.

Command Line:

90

SYBYL Basics

icon’s arrow and select Selected Mol-

ZAP mol_expr

SYBYL-X 1.1


Background images, such as MOLCAD surfaces, associated with the deleted molecules are removed from the screen as well. Delete Atoms Delete the selected atoms. This functionality is enabled on the menubar and icon only if at least one atom has been selected. Menubar: Icon:

Select atom(s) in one or more molecules then Edit > Delete > Selected Atoms Select atom(s) in one or more molecules then Click the Atoms.

Command Line:

icon’s arrow and select Selected

REMOVE ATOM atom_expr

Issue this command for each molecule in which atoms must be deleted, making sure to include the appropriate molecule area within the atom expression. See How to Specify an Atom Expression on page 203. Usage Note: Atoms that are invisible cannot be selected and, therefore, cannot be deleted via this menu item or icon. Unless entire molecules are deleted, the associated background images, such as MOLCAD surfaces, remain on the screen. See also Delete Atoms or Atom Attributes on page 121. Delete Backgrounds Delete one or more backgrounds. This functionality is enabled on the menubar and icon only if at least one background is present. A background is any graphics objects that is not a molecule. Examples are MOLCAD surfaces and ribbons. Menubar:

Icon:

SYBYL-X 1.1

Edit > Delete > Backgrounds (Surface, Ribbon, etc.) Select the background(s) to be deleted or ALL. Click the icon’s arrow and select Backgrounds. Select the background(s) to be deleted or ALL.

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91


Command Line:

BACKGROUND DELETE background_id

Specify the ID number of the background to be deleted or * to delete all backgrounds at once. To find the ID numbers of individual background images type LIST BACKGROUND. Background deletion cannot be undone. Delete Whatever is Selected Delete whatever is selected, atoms, surfaces or both. This functionality is enabled on the menubar and icon only if at least one atom or surface has been selected. Menubar:

Icon:

Select atom(s) in one or more molecules and/or select surface(s) then Edit > Delete > Selected Select atom(s) in one or more molecules and/or select surface(s) then Click to delete all selected objects. If nothing had been selected before clicking the X, nothing will be deleted.

Only atoms, MOLCAD surfaces and ribbons as well as potential surfaces can be selected and deleted in this manner. Read about The Selection Menu and Icons on page 63.

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Chapter 7. Clear and Reset the SYBYL Display Reset Scaling, Translation, and Rotation

7.2 Reset Scaling, Translation, and Rotation 7.2.1 Reset All Reset SYBYL’s graphics window to the original scale, rotation, and translation settings. Menubar: Icon:

View > Transformations > Reset All Click

on the View toolbar.

7.2.2 Reset Selectively Reset all or selective scale, rotation, and translation settings. Icon: Command Line:

SYBYL-X 1.1

Use

on the Miscellaneous toolbar.

STATIC RESET

SYBYL Basics

93

Chapter 7. Clear and Reset the SYBYL Display Undo the Last Operation

7.3 Undo the Last Operation Each molecule area has a single level stack associated with it. Prior to an operation that affects a molecule’s coordinates, or atom and bond definitions, the current state is saved on this stack. If you choose to reverse the action of a command, this data is available to return to the previous state. Menubar: Command Line:

Not accessible from the menubar. RECOVER mol_area UNDO (identical to RECOVER M*)

Notes: 1. The state saved to the stack includes coordinates, atom and bond definitions. 2. UNDO and RECOVER do not reverse the effect of labels or colors. •

If you want to reverse the effect of a labeling operation, use View > Unlabel.

•

You can not reverse the effect of coloring operations. If you have a color scheme you wish to save, you need to save the molecule with that color scheme.

3. The automatic saving to the stack is controlled by the SET AUTOSAVE command (described in the Graphics Manual).

94

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SYBYL-X 1.1

Chapter 8.

Build and Modify Molecules Use the options under the Edit menu (described in Menubar to Command Mapping) to sketch and modify molecules. Use the Sketch Molecule menu option to draw a molecule. The other menu options allow you to add, define, modify, copy, and delete various molecular components. •

Sketch a Small Molecule Tutorial on page 96

•

Ring Fusion Tutorial on page 103

•

Load Fragments on page 109

•

Access the Sketcher on page 111

•

•

SYBYL-X 1.1

•

Sketching Techniques on page 111

•

Sketcher Toolbars on page 115

Modify Molecules Outside of the Sketcher on page 118 •

Atoms on page 118

•

Bonds on page 125

•

Chemical Group on page 128

•

Delete or Modify Substructures on page 129

•

Chirality on page 130

•

Center of Rotation, Name, Type, etc. of a Molecule on page 133

•

Combine (Fuse) Two Molecules on page 134

•


•

Adjust Bond Lengths and Angles to Match Standards on page 135

•

Scan Torsions to Reduce van der Waals Contacts on page 136

•

Create a Molecule by Averaging Existing Molecules on page 136

Define and Modify Geometric Features on page 138

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Chapter 8. Build and Modify Molecules Sketch a Small Molecule Tutorial

8.1 Sketch a Small Molecule Tutorial This tutorial introduces the most common features of SYBYL’s sketcher. See Sketcher Toolbars on page 115 for a full description.

8.1.1 Preface In this tutorial, you will build and minimize Atropine by building the most complex ring system first and then adding the substituents. Typically, molecular fragments from the Standard Fragment Library are used to quickly construct ring systems with good geometry. However, in order to better demonstrate SYBYL’s sketching capabilities, you will use the Sketch Molecule menu items to construct and optimize the most complex ring system.

After completing this tutorial, you will be able to: •

Draw a ring

•

Draw a chain

•

Add substituent groups

•

Check and assign chirality

Before performing the following tutorial you should be familiar with the graphics functions of SYBYL. If necessary, refer to the Quick Reference section in the Graphics Manual for a summary. A Matter of Time: This tutorial requires about 10 minutes of personal time.

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8.1.2 Set Up 1. It is always a good idea to clear the screen and reset the display before starting.

¾

> Delete Everything

¾

Click

¾

Use

on the View toolbar to reset all rotations and translations. on the Display toolbar to set the screen mode to Full.

2. Adjust the tailor setting for cleaning up structures within the sketcher.

¾ ¾ ¾

Options > Tailor In the Tailor dialog, set the Subject to SKETCH. Set the CLEAN_UP option to 6_MINIMIZE

The default is 4_SCAN, which involves non ring bonds only. For this example, the ring systems need to be cleaned up as well and using 6_MINIMIZE will accomplish this by doing an energy minimization of the sketched structure. Any clean up option from 2 to 6 includes all options preceding it in the list, therefore, all non-ring bonds have their bond lengths and angles adjusted, and the torsion angles are scanned and adjusted to relieve bad contacts.

¾

Press Apply then Close.

8.1.3 Enter the Sketching Mode 1. Display the sketch menus and select M1 as the work area in which to build the molecule.

¾

File > New > Small Molecule

A series of toolbars are added to the SYBYL window. You may reposition them along any edge of the SYBYL window. See Sketcher Toolbars on page 115 for a full description. You are automatically placed in Draw mode, as indicated by begin sketching immediately.

, so you can

2. Display a grid to aid in building the molecule to scale. The spacing between grid points is 1.54 Å, the sp3 carbon to sp3 carbon bond length. The grid scales with the molecule in order to show the correct bond length.

¾ SYBYL-X 1.1

Click

to display the grid.

SYBYL Basics

97


Note: If the grid gets in your way, toggle it off by pressing

again.

8.1.4 Sketch the Ring System 1. Build the piperidine ring as follows:

¾

Click in the middle of the screen.

SYBYL displays a “+” representing an unconnected atom. The small box around it indicates that this atom is the current attachment point to which the next sketched atom will be attached.

¾

Click a point above the first atom and approximately one grid spacing to the right (see atom 2 in the figure below).

SYBYL draws a bond to the newly created second atom.

¾ ¾

Continue sketching the 6-membered ring by clicking appropriate points on the screen. Close the ring by selecting atom 1 again.

When you close the ring by picking atom 1, no atom is highlighted, indicating that continuous Draw mode is temporarily deactivated. Continuous mode is always suspended when an existing atom is chosen, whether it is the current atom of attachment or another atom. In the former case, no bond is drawn; while in the latter case, a bond is drawn and then continuous draw mode is deactivated.

2. Change the type of atom 1 to a nitrogen.

¾ ¾ ¾

On the second toolbar (showing various atomic symbols), click N. On the first toolbar, click

.

Click atom 1 on the sketched molecule.

SYBYL displays a label indicating that the type has been successfully changed and the atom is colored blue.

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3. Introduce a third dimension to the molecule.

¾

Click and hold down the Left mouse button and drag the cursor up to rotate the molecule about the X axis until it has an orientation similar to that shown in the figure below.

4. Add the bridge across the ring.

¾ ¾ ¾ ¾

On the second toolbar, click C then click mode.

to go back to draw

Click atom 2 to make it the current attachment atom. Click a point below atom 2 and then another point diagonal to the new atom. Click atom 6 to close the ring.

5. Move carbon 4 down to give the ring a chair conformation.

¾

Click , then on atom 4 then on a point below it and below the plane of the ring.

6. Clean up the ring system.

¾

On the first toolbar, click

.

The molecule’s geometry is optimized quickly using the Tripos force field.

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8.1.5 Add a Chain 1. Center the molecule on the screen.

¾ ¾

Click

to center the molecule.

Rotate the molecule until its orientation is similar to that shown in the figure below.

2. Add a carbon chain to the ring.

¾ ¾ ¾

Click atom 4 as the new attachment atom. Sketch the chain by clicking successive points at approximate locations on the screen for atoms 9 through 13. Click atom 13 again to deactivate continuous Draw mode and end the chain.

3. Draw a double bond for the carbonyl group.

¾ ¾

Click atom 10 as the new point of attachment and then click a point above the atom. Click atom 10 again.

The double bond appears and continuous Draw mode is deactivated, since an existing atom was chosen. 4. Add a carbon to the nitrogen.

¾ ¾

Click atom 1 (N), then a point to its left. Click that new atom again to deactivate continuous Draw mode.

5. Sketch the ester and hydroxyl groups.

¾

100

On the second toolbar, click O then click

SYBYL Basics

.

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¾

Click each of the three atoms: 9, 13, and the end of the double-bond. The atoms are labeled with an O and colored red to reflect the change.

8.1.6 Add a Phenyl Group 1. Add a phenyl ring to the molecule.

¾ ¾

On the third toolbar (showing various groups), click PHENYL. In the structure, click atom 11.

2. Center the molecule.

¾ ¾

Click

.

Compare your sketch with atropine.

8.1.7 Check the Chirality Make sure that atom 11 has a chirality of S.

¾ ¾

Click

and click atom 11.

In the console type S and press the Enter key.

If atom 11 is already an S chiral center, a message is displayed in the console informing you of this and nothing else happens. If, however, the R chiral center has been sketched, the center is inverted to assume the proper stereochemistry.

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8.1.8 Clean Up the Model 1. Clean up the model.

¾

Click

.

2. Add the necessary hydrogens to all unfilled valences.

¾

Click

to fill all open valences with hydrogens.

All atom and bond types are automatically converted to SYBYL types, based on the connectivity prior to adding hydrogens. 3. Exit the sketching mode.

¾

On the first toolbar click EXIT.

A final clean up is done automatically when you exit the sketcher.

8.1.9 Save the Sketched Molecule 1. Name the molecule.

¾ ¾

Click on any atom then Edit > Molecule > Name Type atropine and press OK.

2. Save the full description of the molecule in a text file.

¾ ¾ ¾ ¾


)

In the Save Molecule dialog, by default, atropine appears in the File field. By default, the Format is set to MOL2. Press Save.

A file named atropine.mol2 is created in the current directory. 3. This concludes the small molecule sketching tutorial. In this tutorial, you built and minimized atropine by building the most complex ring system first and then adding the substituents.

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Chapter 8. Build and Modify Molecules Ring Fusion Tutorial

8.2 Ring Fusion Tutorial The following tutorial illustrates several examples of fusions: •

Fuse Two Planar Bonds

•

Fuse Two Rings to Build a Spiro System

•

Fuse Two Non Planar Bonds

•

Fuse A Planar Bond With A Non Planar Bond





¾ ¾



8.2.2 Fuse Two Planar Bonds The fusion of two planar systems requires only two pair of atoms. In this example, furan (M1) is fused to pyridine (M2) and the resulting model appears in M2. 1. Read in the two fragments, color them by atom type, and label both structures.

¾ ¾ ¾ ¾

File > Get Fragment Select FURAN and press OK. File > Get Fragment Select PYRIDINE and press OK.

2. Set the Screen mode to display the molecules side by side.

¾

Use

on the Display toolbar to set the screen mode to Half.

3. Label the atoms by ID numbers.

¾ SYBYL-X 1.1

Use

on the View toolbar to label the Molecules by Atom ID.

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4. Fuse the two structures.

¾ ¾ ¾ ¾

In the console, type: fuse Click atom 6 in pyridine, and then atom 2 in furan to form the first pair. Click atom 5 in pyridine, and then atom 3 in furan to form another pair. In the Select Atom dialog, press End. Furan is fused to pyridine. The molecule whose atom was selected first (pyridine) to perform the ring fusion is updated.

8.2.3 Fuse Two Rings to Build a Spiro System You can specify a spiro fusion by first selecting the two atoms that become the spiro center. The second pair involves a ring atom in one molecule and a hydrogen in the other. 1. Clear the SYBYL screen.

¾

> Delete Everything

2. Read in the two molecules.

¾ ¾ ¾ ¾

File > Get Fragment Select 4H-PYRAN and press OK. File > Get Fragment Select PIPERIDINE and press OK.

3. Label the atoms by ID numbers.

¾

Use

to label the Molecules by Atom ID.

4. Fuse the two rings.

¾ ¾ ¾

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In the console, type: fuse Click atom 4 in piperidine, and then atom 4 in 4H-pyran to form the first pair. Click atom 12 in piperidine, and then atom 5 in 4H-pyran to form another pair.

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¾

In the Select Atom dialog, press End.

The two rings are fused with a spiro center; the resulting model appears in M2.

8.2.4 Fuse Two Non Planar Bonds In the following steps, you will fuse tetrahydropyran (M1) to piperidine. Several methods are used by providing: •

Two pair of atoms (result in M2),

•

Three pair of atoms (result in M3),

•

Four pair of atoms (result in M4).

1. Clear the SYBYL screen.

¾

> Delete Everything

2. Load the molecules and label the atoms.

¾ ¾ ¾ ¾ ¾ ¾

File > Get Fragment Select TETRAHYDROPYRAN and press OK. File > Get Fragment Select PIPERIDINE and press OK. Use

to set the screen mode to Quartered.

Double-click any atom in piperidine to select the entire molecule.

¾

Edit > Copy (or click

¾

Select M3: and press OK.

¾ ¾ ¾

Click

on the Edit toolbar).

, and press OK to accept M4: as the destination.

Click away from all molecules to clear the selection. Use


3. Use two pair of atoms to fuse two non planar bonds. SYBYL resolves the ambiguity automatically by selecting the alternative which gives rise to the best fusion geometry. The results are displayed in M2.

¾

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In the console, type: fuse

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¾ ¾ ¾

Click atom 6 in piperidine (in M2), and then atom 3 in tetrahydropyran to form the first pair. Click atom 5 in piperidine (in M2), and then atom 2 in tetrahydropyran to form another pair. In the Select Atom dialog, press End.

Two non planar bonds are fused. The resulting model with extraneous hydrogens appears in M2, showing that the selection of two atom pairs was insufficient for this type of fusion. 4. Use three pair of atoms to fuse two non planar bonds. As in the previous steps, SYBYL automatically resolves the ambiguity. The results are displayed in M3.

¾ ¾ ¾ ¾ ¾

In the console, type: fuse Click atom 6 in piperidine (M3), and then atom 2 in tetrahydropyran (M1) to form the first pair. Click atom 5 in piperidine (M3), and then atom 3 in tetrahydropyran (M1) to form a pair. Click atom 16 in piperidine (M3), and then atom 1 in tetrahydropyran (M1) to form a pair. In the Select Atom dialog, press End.

Two non planar bonds are fused; the resulting model appears in M3. 5. Use four pair of atoms to fuse two non planar bonds. The results of the fusion are displayed in M4. Manual fitting of the two bonds to be fused reveals that the torsional angles of the four atoms involved are 60° in piperidine and -60° in tetrahydropyran. In order to produce a geometry better suited for the cis fusion you want to perform, tetrahydrofuran is inverted first.

¾ ¾ ¾ ¾ ¾

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Edit > Chirality > Invert Select M1:tetrayhydropyran from the pull-down. Press the

icon and press OK.

Clear the atom selection. In the console, type: fuse

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¾ ¾ ¾ ¾ ¾

Click atom 6 in piperidine (M4), and then atom 2 in tetrahydropyran (M1) to form the first pair. Click atom 5 in piperidine (M4), and then atom 3 in tetrahydropyran (M1) to form a pair. Click atom 16 in piperidine (M4), and then atom 1 in tetrahydropyran (M1) to form a pair. Click atom 15 in piperidine (M4), and then atom 4 in tetrahydropyran (M1) to form a pair. In the Select Atom dialog, press End.

Two non planar bonds are fused; the resulting model appears in M4.

8.2.5 Fuse A Planar Bond With A Non Planar Bond 1. Load the molecules and label the atoms.

¾ ¾ ¾ ¾ ¾

> Delete Everything File > Get Fragment Select HEXAHYDROAZEPINE and press OK. File > Get Fragment Select BENZENE and press OK.

¾

Use

to set the screen mode to Half.

¾

Use


2. Fuse benzene (M2) to hexahydroazepine (M1) to form a model in M1.

¾ ¾ ¾ ¾

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In the console, type: fuse Click atom 5 in hexahydroazepine (M1), and then atom 1 in benzene (M2) to form the first pair. Click atom 4 in hexahydroazepine (M1), and then atom 2 in benzene (M2) to form a pair. In the Select Atom dialog, press End.

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The planar bond is fused with a non planar bond. Notice the poor quality of the geometry at the ring fusion and the fact that extraneous hydrogens are left over from the hexahydroazepine. Clean up and minimization are necessary before this model could be used. The best strategy to assure the quality of the fusion and reduce the need for minimization is to make sure that the geometry of the bonds to be fused is identical in both molecules before the fusion occurs. 3. Set the Screen mode to full.

¾

> Delete Everything

¾

Use

to reset all rotations and translations.

¾

Use

to reset the screen mode to Full.

This concludes the Ring Fusion Tutorial.

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Chapter 8. Build and Modify Molecules Load Fragments

8.3 Load Fragments SYBYL provides a library of fragments from which you can easily build most molecules. The following table describes information for using the menubar or command line to select and display fragments contained in the Fragment Library. Menubar:

File > Get Fragment • Select one fragment in the list. The fragment will be loaded into the first empty molecule area.

Use the Fragment Library search menu via Command Line:

FRAGMENT MENU menu_choices mol_area

Load a Single Fragment by name via Command Line:

FRAGMENT NAME name [mol_area]

SYBYL-X 1.1

•

menu_choices—Series of numbers, typed at the keyboard, identifying successive menu items. • mol_area—Area to receive selected fragment, current contents are overwritten. Menus are hierarchical and categorize various molecular fragments according to structure and/or function. The DATABASE SEARCH command, for example, uses a menu structure to control searching of a database. Enter number of menu items to move up or down the hierarchy until desired molecule is found. Typing the number of an actual molecule retrieves that molecule. There are also three words that are valid choices: • TOP—Return to top level of menu hierarchy, where the most general categories are displayed. • UP—Back up one level in the hierarchy to a set of more general categories. • QUIT—Exit from search procedure without choosing a molecule. •

name—Name (with optional wildcards) of fragment to retrieve. • mol_area—Area to receive the fragment. For example, FRAGMENT NAME BENZENE M1 retrieves the fragment BENZENE into M1. FRAGMENT NAME VIT*B2 M1 retrieves the fragment Vitamin B2 into M1 (because only one fragment satisfies the expression VIT*B2).

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Chapter 8. Build and Modify Molecules Load Fragments

Load Multiple Fragments from Library via Command Line:

FRAGMENT NAME name_expr [QUIT|RETRIEVE|SELECT|UNSELECT]

•

name_expr—Name (with optional wildcards) specifying multiple fragments to retrieve. If no fragment is found or if single fragment is retrieved, no further input necessary (i.e., entering one of the following items is skipped). • QUIT—Exit search procedure without choosing a molecule. • RETRIEVE [mol_area]—Retrieve multiple fragments starting with specified mol_area. • SELECT [name_expr]—Select subset of currently chosen molecules according to their names. • UNSELECT—Unselect list of fragments. This undoes previous SELECT operation, thus allowing a more flexible search of the library. It can be applied any number of times. For example, FRAGMENT NAME BE* RETRIEVE M1 retrieves all fragments starting with the letters BE and places them in consecutive molecule areas starting with M1.


110

•

Libraries of Chemical Groups and Fragments on page 231.

•

Load a Molecule from the Fragment Library: on page 16 for an example exercise.

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Chapter 8. Build and Modify Molecules Access the Sketcher

8.4 Access the Sketcher Menubar:

File > New > Small Molecule or Edit > Molecule > Sketch See Sketcher Toolbars on page 115.

Toolbar Icon: Command Line:

on the Molecule toolbar. SKETCH mol_area

File > New > Small Molecule always uses the first empty molecule area. Edit > Molecule > Sketch and follows:

determine the molecule area to use as

•

If nothing is selected, the Sketcher uses the first empty molecule area.

•

If one or more atoms are selected in the same molecule area, the Sketcher is launched for that molecule area. This is how to use the Sketcher to modify an existing molecule.

•

If atoms were selected in multiple molecule areas you will be prompted to specify which molecule area the Sketcher will operate on.

•

Additionally, any hidden atoms in the selected molecule are made visible upon invoking the Sketcher.

Molecules are drawn flat until you rotate the structure. Any atom added subsequent to a rotation assumes the transformed Z-coordinate of the atom to which it is bonded. Unconnected atoms are always two-dimensional since there is no reference point. •

Sketching Techniques on page 111

•



Edit > Clean-Up Molecule > 3D Geometry (Concord) for fast conversion of 2D coordinates to 3D (in the Concord Manual).

•

TAILOR SET GRID to customize the displayed grid.

8.4.1 Sketching Techniques The following sections discuss some basic ideas and helpful techniques for using the Sketcher. You can start sketching with an atom or a fragment. Important: You can not start sketching with a chemical group.

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Always Review the Sketched Model Although flexible enough to enable building any structure, the Sketcher does have enough chemical sense to warn you when you have done something unnatural. For example, SYBYL displays a message if the valence of an atom is about to be exceeded. It is your decision to continue or not. About Continuous Drawing Mode You can stop the continuous drawing mode (also referred to as “pen up movement”) by doing one of the following: •

To cancel the selection of a point of attachment, click the last atom drawn. You can then move the cursor to another part of the molecule without drawing a bond. When you pick a new point of attachment, continuous drawing mode is turned on again.

•

Click an existing atom. A bond is drawn from the current atom to this existing atom and then the pen up movement is initiated.

Atomic Symbols Only SYBYL designates the atom types with only the atomic symbols, in order to eliminate the burden of having to decide the proper SYBYL atom type. Atom Types You can change the atom types in two different ways: Method One: Change the default atom type, before adding the new atom to the model: 1. On the second toolbar, click the desired atomic symbol. If the atom type is not listed, click More to display a periodic table and select the desired atomic symbol. The table is color-coded using the SYBYL atom type coloring scheme. Once a selection is made, click X in the upper corner to close the table. (Note that the selected atomic symbol now appears as a button below the More button in the toolbar.) 2. Click in the display area to add a new atom of that type. Subsequent atoms have the new atom type until you select a different atomic symbol. Use this technique if you want to draw a chain of atoms, other than carbons.

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Method Two: Modify the type of an existing atom: 1. On the second toolbar, click the desired atomic symbol. If the atom type is not listed, click More to display a periodic table and select the desired atomic symbol. The table is color-coded using the SYBYL atom type coloring scheme. Once a selection is made, click X in the upper corner to close the table. (Note that the selected atomic symbol now appears as a button below the More button in the toolbar.) 2. On the first toolbar, click

.

3. Click the atom whose type you want to change. SYBYL updates the atom type. Branching To draw an atom not connected to the last atom displayed, a pen up action must be signified by choosing this last (highlighted) atom again. SYBYL removes the highlighting and temporarily turns off the continuous draw mode. When you choose a new point of attachment, SYBYL automatically turns the continuous drawing mode on and you can add a new chain of atoms. If you select a point of attachment in error, click that atom again to initiate the pen up movement. You can now select a new point of attachment. Edit Existing Molecules Existing molecules or fragments can be brought into the sketcher in order to make quick modifications. When the sketcher is exited or the clean-up option selected, only the part of the molecule that changed is cleaned up. The rest of the molecule maintains its current geometry. You can disable this option by setting TAILOR SET SKETCH AGGREGATES to OFF. With this option, the whole molecule is considered in the clean up phase. Label and Color In order to make different atom types easily identified, heteroatom labeling and molecule color, coded by atom type, are the sketcher defaults. Multiple Bonds Draw the single bond, then do one of the following: •

SYBYL-X 1.1

If the last atom drawn is one of the atoms involved in the double bond, select the target atom and a second line appears between the two atoms designating the double bond. Since the target atom is an existing atom,

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continuous drawing mode is temporarily turned Off and a new point of attachment must be chosen before drawing commences again. •

If neither atom defining the double bond is currently selected, turn Off continuous drawing mode by picking the last atom drawn a second time. Select one of the atoms of interest as the new point of attachment. Pick the target atom for the double bond and a double line appears between the two atoms. As mentioned above, since the target atom is an existing atom, drawing mode is temporarily suspended.

The same strategy can be repeated for sketching triple bonds. Aromatic bonds are designated by alternating single and double bonds within the ring. Rings Sketch the backbone on the ring by picking points at appropriate positions on the screen. To close the ring select the first atom of the ring again, thereby causing a bond to be drawn between this atom and the last atom drawn. Since this ring closure atom is an existing atom, SYBYL temporarily stops the continuous draw mode, so you can choose a new point of attachment. To add a bond to the current atom, select that atom again. Z Coordinate To add a third dimension to the molecule, apply rotations to the model. Once an atom has a Z-coordinate, any subsequent atoms attached to it are drawn in the same Z-plane. For example, if a rotation precedes moving an atom ( ), the atom being moved is drawn in a different plane from the rest of the molecule. Many different conformations of a molecule can be achieved with this method, such as chair or boat cyclohexane.

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8.4.2 Sketcher Toolbars Accesses: •

File > New > Small Molecule

•

Edit > Molecule > Sketch

•

on the Molecule toolbar.

Usage Notes: •

To build upon a chemical fragment you must retrieve the fragment before accessing the Sketcher. See Load Fragments on page 109.

•

The clean up method to be used when exiting the Sketcher must specified before accessing the Sketcher. See TAILOR SET SKETCH CLEAN_UP in the Tailor Manual. The default method (4_SCAN) fixes non-cyclic bond lengths and valences angles and rotates non-cyclic bonds to escape atomic overlaps.

The Sketcher has 3 toolbars of icons grouped as follows: •

Sketching Functions — Activities necessary to sketch a structure. See Sketching Functions Toolbar below for descriptions.

•

Atomic Symbols — Pick one of these atomic symbols to indicate the atom type to draw. If the atom type is not listed, click More to display a periodic table and select the desired atomic symbol. The table is colorcoded using the SYBYL atom type coloring scheme. Once a selection is made, click X in the upper corner to close the table. (Note that the selected atomic symbol now appears as a button below the More button in the toolbar.)

•

Groups — Substructures defined in the Group Library. Groups have predefined attachment points. (Refer to Group Library Structure and Contents on page 232 for more information.) Usage Note: you cannot start sketching with a chemical group. An atom must exist as an attachment point before a functional group can be added.

A toolbar can be moved to the top or the right side of the display area by clicking on the dashed line and dragging it to the new location. Toolbars can be reordered by dragging one at a time to the last position (closest to the display area). You can also combine toolbars by dragging one over the other. (This is what always occurs if you move more than one toolbar to the top of the display area.)

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Sketching Functions Toolbar Activates the continuous drawing mode, the default action, with the cursor defined as a carbon atom. To draw a chain of carbons: • Click a point on the screen where the first atom is to be located; a cross appears. • Click another point on the screen; that point appears and SYBYL draws a line (bond) between the two atoms. • Continue clicking until you reach the desired chain. Note that the current atom of attachment is always highlighted. Places you in modify mode. Clicked atoms are replaced by the atom selected in the second toolbar. Prompts you for the atom to move and its new location. The atom, and all bonds connected to it, are moved to the new location. This mode remains active until you select another option. This capability is useful when building a particular conformer. Deletes the current sketch molecule. Removes a bond from the drawn structure. You must select two bonded atoms. Undoes the last operation, restoring the molecule to its previous state. Note: If you want to reverse the effect of the LABEL command, use UNLABEL. Centers the molecule on the screen. Adjusts molecule geometry according to the method specified via the TAILOR SET SKETCH CLEAN_UP command. Also determines the proper atom hybridization, based upon bond type and atom type of connected atoms. No matter which option is chosen for clean-up, the atom and bond type conversion is always done. Adds hydrogens to all unfilled valences. Removes all hydrogens in the sketched molecule. Deletes atoms, and any bonds connected to them, from the molecule being sketched. This mode remains active until you select another option. Specifies whether a chiral center is R or S.

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Modifies the torsion angle of four connected atoms. Modifies the bond angle of three connected atoms.

EXIT

SYBYL-X 1.1

Toggles the grid on and off. Use the grid to aid sketching. Spacing between grid points is 1.54 Å, the approximate length of a carbon-carbon single bond. Performs clean up procedure and assigns SYBYL atom types (see description for the clean up tool).

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Chapter 8. Build and Modify Molecules Modify Molecules Outside of the Sketcher

8.5 Modify Molecules Outside of the Sketcher •

Atoms on page 118

•

Bonds on page 125

•

Chemical Group on page 128

•

Delete or Modify Substructures on page 129

•

Chirality on page 130

•

Center of Rotation, Name, Type, etc. of a Molecule on page 133

•


•


•

Adjust Bond Lengths and Angles to Match Standards on page 135

•

Scan Torsions to Reduce van der Waals Contacts on page 136

•

Create a Molecule by Averaging Existing Molecules on page 136

8.5.1 Atoms Add an Atom to an Existing Structure Menubar: Command Line:

Edit > Atom > Add Connected Atom ADD ATOM attachment_atom type

• •

attachment_atom—Atom to which new one is bonded. type—New atom’s chemical type and hybridization. (Type “?” at prompt to list available atom types.)

SYBYL automatically determines the coordinates, based on bond length and bond angle data from parameter tables. Add a Standalone Atom Menubar: Command Line:

Edit > Atom > Add Standalone Atom ADD RAWATOM mol_area name type x y z

• •

• •

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mol_area—Area to receive new atom. name—Name for new atom (must start with an alphabetic character and contain only alphabetic characters, digits, and/or the special symbols dollar sign ($), underscore (_), or apostrophe (')). type—Chemical type and hybridization of atom. (Type “?” at prompt to list available atom types.) x, y, z—Coordinates of atom.

SYBYL-X 1.1


Position the atom by specifying coordinates or by using the mouse. Add a Chain of Atoms of the Same Type Menubar: Command Line:

Edit > Atom > Add Chain of Atoms ADD CHAIN ATTACH | REPLACE [atom] type length • ATTACH—Add new chain to specified atom with appro-

•

• • •

priate geometry. REPLACE—Remove specified atom and add new chain in its place, with ideal geometry (useful when hydrogens are present). atom—Atom for attachment or to replace. type—Chemical type and hybridization of atoms in chain. (Type “?” at prompt to list available atom types.) length—Length of chain to create, may vary from 1 upward (no upper limit). “1” is equivalent to the ADD ATOM command.

SYBYL attaches chains to the existing structure with ideal geometry. SYBYL determines the coordinates of all atoms from the parameter tables. Add Pseudo-atoms (Centroids) Pseudo-atoms (centroids) are added to prochiral, methyl, and phenyl ring groups. They are often used for defining constraints to the prochiral, methyl, or aromatic protons. Constraints are needed when you do not have stereospecific resonance assignments for prochiral atoms (or methyl pairs, such as in leucine and valine), or when fast motions are present (such as methyl rotors and aromatic ring flipping). Menubar: Command Line:

Edit > Atom > Add Pseudo-atoms ADD_PSEUDOATOMS mol_area

The dummy atom’s name at the centroid position is defined according to the nomenclature first presented in Kurt Wüthrich, NMR of Proteins and Nucleic Acids, J. Wiley and Sons, 1986. For example, the beta methyl group on alanine is named “QB”. The algorithm identifies appropriate atom sets, independently of the substructure and atom names. For example, any pair of protons bonded to a “heavy” atom, and that are not part of methyl groups, will have a pseudo-atom added between them.

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Add Hydrogens Fill all empty valences with hydrogens. If the molecule is a protein, nucleic acid, or saccharide, the Biopolymer functionality, BIOPOLYMER ADDH, is exercised first. See License Requirements for SYBYL Basics on page 8. Hydrogens added to invisible atoms are automatically made invisible. Menubar:

Icon:

Command Line:

Edit > Hydrogens > Add All Hydrogens Edit > Hydrogens > Add Polar Hydrogens Edit > Hydrogens > Add Non-Polar Hydrogens Adding hydrogens works on whole molecule areas, affecting only those containing selected atoms or all of them is nothing is selected. The {POSSIBLE_HBOND} built-in set is used to identify polar hydrogens. on the Display toolbar. Add all hydrogens to molecule areas containing selected atoms or to all of them if nothing is selected. FILLVALENCE atom_expr H

•

atom_expr—Atoms to have empty valences filled with hydrogens.

SYBYL sets bond lengths and angles to standard values determined from the parameter file (described in the Force Field Manual). Hydrogens, when added, acquire the rendering mode of the atoms they are attached to. Fill Empty Valences with any Atom Type Menubar: Command Line:

Not accessible from the menubar. FILLVALENCE atom_expr atom_type

• •

atom_expr—Atoms to have empty valences filled. atom_type—Mnemonic type of atom to use in filling valences.

SYBYL sets bond lengths and angles to standard values determined from the parameter file.

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Delete Atoms or Atom Attributes Delete All Hydrogens: Edit > Hydrogens > Delete All Hydrogens Deleting all hydrogens works on whole molecule areas, affecting only those containing selected atoms or all of them is nothing is selected. Delete Selected Atoms: Menubar and toolbar require pre-selection of atoms. Menubar: Toolbar:

Edit > Delete > Selected Atoms

Command Line:

REMOVE ATOM atom_expr

> Selected Atoms

Deleting atoms also removes all bonds involving the deleted atom(s) and any features (normal, plane, constraint) attached to them. SYBYL renumbers atoms and bonds to reflect the removal of objects from the molecular description. If the removed atom is a member of a static set, the set membership is updated. Removing all atoms is equivalent to deleting the molecule. Delete a Connected Group of Atoms: Use the Split functionality to remove a portion of a molecule by specifying two bonded atoms: Menubar:

Not accessible from the menubar.

Command Line:

SPLIT origin_atom target_atom

SYBYL deletes the bond between the specified atoms along with all atoms on the target side of that bond. Note: You can not use the Split functionality if the indicated bond is in a ring. You must first break the ring by removing a bond or an atom. Delete Atom Attributes: Attributes can be removed from one or more atoms without deleting the atom itself. Command Line:

SYBYL-X 1.1

REMOVE ALL_ATOM_ATTRS atom_expr

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Modify an Atom Menubar: Change Point Charge via Command Line: Change Coordinates:

Edit > Atom > Modify MODIFY ATOM CHARGE atom_expr charge

MODIFY ATOM COORDINATES atom_expr xyz_coord

Changes are not restricted by the bond length table nor by atoms being in rings. Coordinates are unconditionally altered. Update Lone Pairs:

MODIFY ATOM LONE_PAIR atom_expr

Lone pair positions may need to be updated after whole or partial structural changes are made to the molecule, such as minimizations. Geometry optimizations using Tripos force field do not affect lone pair positions. Use this command before defining an extension point if any atoms involved are lone pairs. Change Name:

MODIFY ATOM NAME atom_expr APPEND_AUTO|QUERY|SEQUENTIAL_AUTO • APPEND_AUTO—Supply a single string to concate-

nated with current name for each selected atom. QUERY—Prompts for name for each selected atom. SEQUENTIAL_AUTO—For each selected atom, concatenate name of atomic element with the atom ID number to form new name. First character of name must be alphabetic. All others must be alphabetic, numeric, or the apostrophe.

• •

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Change Only Type (not Geometry):

MODIFY ATOM ONLY_TYPE atom_expr {type}

Recalculate Extension Points/Lone Pairs:

MODIFY ATOM SYBYL_POINTS atom_expr

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Prompts for the type for each specified atom. SYBYL modifies the types of bonds associated with the atoms to fit the new atom types. The geometry around atoms or atom names is not changed. TAILOR SET ATOM_TYPE FIX_NAMES sets whether atom names are affected by changes to an atom’s type. Use if extension points/lone pairs become distorted during other calculations.

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Change Type and Geometry:

Assign Alternate Types

MODIFY ATOM TYPE atom_expr {type}

Prompts for the type for each specified atom. After all new types have been entered, SYBYL modifies the types of associated bonds to fit the new atom types. For non-ring atoms, SYBYL also adjusts bond lengths. Bond lengths and types are taken from $TA_ASCTABLES/BOND_LENGTHS and BOND_TYPES. If the bond type is ambiguous (i.e., there is more than one possible bond type to connect the two atom types) or unknown, you are prompted. You can rename atoms by preserving the suffix and replacing the old atomic symbol with the new one. This prevents situations such as replacing a carbon labeled C8 with a nitrogen, and the label is still C8. TAILOR SET ATOM_TYPE FIX_NAMES sets whether atom names are affected by changes to an atom’s type. MODIFY ATOM OTHER_TYPES set_name ASSIGN SPECIFIC|UNKNOWN • set_name—Set of alternate atom types: KOLL_ALL, KOLL_UNI, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL, or MMFF94. • SPECIFIC—Specify atoms to assign types to. You

are prompted for the atom types, one at a time, as the atom is highlighted. • UNKNOWN—Prompts for atom types for each atom in molecule which does not have an alternate atom type. Licensing: See License Requirements for SYBYL Basics on page 8. Assign Alternate Type via SLN

MODIFY ATOM OTHER_TYPES set_name SLN_AUTO_ASSIGN SPECIFIC|UNKNOWN

•

Unassign Alternate Types

•

set_name—Set of alternate atom types: KOLL_ALL, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL. SPECIFIC—Specify atoms to assign types to.

•

UNKNOWN

MODIFY ATOM OTHER_TYPES set_name UNASSIGN atom_expr • set_name—Set of alternate atom types: KOLL_ALL, KOLL_UNI, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL, or MMFF94.

SYBYL will use the default (dictionary) value for the alternate atom type instead of user-assigned value.

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Label Alternate Types

MODIFY ATOM OTHER_TYPES set_name LABEL mol_area • set_name—Set of alternate atom types: KOLL_ALL, KOLL_UNI, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL, or MMFF94.

Menubar: View > Label > Molecules > Atom Type (applies to pre-selected atoms or to all molecule areas if no atoms were selected). See Label in the Graphics Manual. Licensing: See License Requirements for SYBYL Basics on page 8. Unlabel Alternate Types

MODIFY ATOM OTHER_TYPES set_name UNLABEL mol_area • set_name—Set of alternate atom types: KOLL_ALL, KOLL_UNI, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL, or MMFF94.

List Alternate Types

MODIFY ATOM OTHER_TYPES set_name LIST SPECIFIC|UNKNOWN|USER_ASSIGNED • set_name—Set of alternate atom types: KOLL_ALL, KOLL_UNI, AMBER7_FF02, AMBER7_FF99, AMBER95_ALL, or MMFF94. • SPECIFIC—List alternate types of all specified

• •

atoms, including source of alternate type (userspecified, or default—from macromol dictionary). UNKNOWN—List names of all atoms with unknown alternate atom types. USER_ASSIGNED—List types of all atoms with userassigned alternate types.

Alternate atom types can come from two sources: the macromol dictionary (also referred to as the default source) or user input. Alternate atom types are needed for energy calculations using non-Tripos force fields. MODIFY ATOM OTHER_TYPES displays or lists alternate atom types from either source, and allows input of user-assigned alternate types. User-assigned types are stored with the molecule, and take precedence in force field calculations over dictionary-supplied alternate atom types. Currently supported alternate atom type sets are: •

124

Kollman all-atom (KOLL_ALL) and Kollman united-atom (KOLL_UNI) force fields. A list of Kollman atom types is provided in the Force Field Manual. Note: Alternate atom types must be defined for both KOLL_UNI and KOLL_ALL force fields for energy setup to work. If the atom type is defined for only one, the ENERGY, MAXIMIN2, and DYNAMICS SETUP commands all fail with an error condition.

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•

AMBER7 FF99 (AMBER7_FF99) force field, which is essentially AMBER95 atom types with a few types added. A list of AMBER7 FF99 atom types is provided in the Force Field Manual.

•

AMBER7 FF02 (AMBER7_FF02) force field, which is essentially AMBER7 FF99 atom types with different charges and polarization included. A list of AMBER7 FF99 atom types is provided in the Force Field Manual.

•

AMBER 95 (AMBER95_ALL) force field.

•

MMFF94 force field. A list of MMFF94 atom types is provided in the Force Field Manual.


The Load Charges section of the Biopolymer Manual to load atomic charges and alternate atom types from the dictionary.

8.5.2 Bonds Add Bonds Manually Menubar:

Edit > Bond > Add Atom By Atom Repeats adding bonds until End is selected.

Command Line:

ADD BOND origin_atom target_atom

• •

origin_atom—Atom at beginning of bond. target_atom—Atom at end of bond.

The bond type of the new bond is set by the atom types at its endpoints. If there is ambiguity regarding the bond type, a prompt asks for the resolution. Atomic positions are not altered by adding a bond. Add Bonds Automatically Single bonds may also be added using the Quick Bonds functionality. SYBYL adds a single bond between two atoms if the distance between them is within an acceptable range. This is particularly useful for PDB files containing disconnected HETATM records. Menubar: Command Line:

Edit > Bond > Add Quick Bonds QUICKBOND mol_area atom_expr

• •

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mol_area—Work area containing the molecule. atom_expr—Atoms between which connectivities must be identified.

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SYBYL adds a bond between two atoms, A and B, if the distance between them, DISTAB, is within acceptable range: Ideal_Bond(1-Tol_Neg) < DistAB < Ideal_Bond (1+Tol_Pos) where:

[EQ 1]

•

Ideal_Bond—Standard bond length between atom types A and B in the bond length table.

•

Tol_Neg—Tolerance used to determine low end of the distance range. This Tailor variable has a default of 0.30.

•

Tol_Pos—Tolerance used to determine high end of the distance range. This Tailor variable has a default of 0.10.

The asymmetry of the acceptance window (Tol_Neg > Tol_Pos) allows for alkynes (Ideal_Bond = ~1.15 Å) and certain short aromatic C-C bonds to be recognized as bonds without making chemical oddities from non-covalent intramolecular hydrogen bonding patterns. By adding only single bonds, molecular connectivity can be determined with a high degree of accuracy and minimum user intervention. Check all atom and bond types within the specified atom expression before proceeding with calculations, where this information is relevant. Additional Information: •


•

TAILOR SET CONNECT to alter the characteristics of the connectivity

determination. Delete Bonds Menubar and toolbar do not require pre-selection, but will act on pre-selected atoms by deleting the bond(s) between them. Menubar: Toolbar:

Edit > Delete > Bonds

Command Line:

REMOVE BOND bond_expr

> Bonds

Features (rotatable bonds) associated with the deleted bond are removed as well. Bonds are renumbered to reflect the removal of objects from the molecular description. If one of the two last atoms in a substructure is a biopolymer atom (as defined in the macromol dictionary), SYBYL retains the root atom in the substructure and the other atom in the substructure zero.

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Delete Bond Attributes Attributes can be removed from one or more bonds without deleting the bonds themselves. Command Line:

REMOVE ALL_BOND_ATTRS expression

Modify a Bond Modify Type via the Menubar: Modify Type via Command Line:

Modify Length via the Menubar: Modify Length via Command Line: Modify Angle via the Menubar: Modify Angle via Command Line: Modify Torsion via the Menubar: Modify Torsion via Command Line:

Edit > Bond > Modify Type MODIFY BOND AUTO_TYPE|TYPE bond_expr {type} • AUTO_TYPE—Force the automatic determination

of bond type according to types of atoms at each end of the bond. Only prompts for bonds whose types are ambiguous. • TYPE—Prompt for type for each specified bond. No adjustment of parameters other than type is attempted for selected bonds. Edit > Bond > Modify Distance MODIFY DISTANCE atom1 atom2 value

Edit > Bond > Modify Angle MODIFY ANGLE atom1 atom2 atom3 angle

Edit > Bond > Modify Torsion MODIFY TORSION atom1 atom2 atom3 atom4 angle

When changing the length, angle, or torsion, SYBYL alters the coordinates of last specified item and all atoms attached to it. The atoms must be connected to form a bond, angle, or torsion, respectively. If the bond, angle, or torsion is in a ring, an error is reported and no alteration is made.

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8.5.3 Chemical Group You can add a functional group to the molecular structure and have their geometry determined from the parameter tables. The atoms in the group and their relative positions are read from the Group Library. Menubar: Command Line:

Not accessible from the menubar. ADD GROUP group_name ATTACH | REPLACE atom

• • •

•

group_name—Name of group to add to structure. (Type “?” at prompt to list available groups.) ATTACH—Add new group to specified atom with appropriate geometry. REPLACE—Remove specified atom and add new group in its place, with ideal geometry (useful when hydrogens are present). atom—Atom for attachment or to replace.

The permission on the Group Library should normally be “read only” to prevent accidental modification. However, the Group Library is user expandable, and before adding a group to this library, you must change the permission on the file $TA_DATA/GROUP to allow writing: chmod +w $TA_DATA/GROUP Set the permission back to read only after the group has been added: chmod -w $TA_DATA/GROUP Additional Information: •

128

See Group Library Structure and Contents on page 232.

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8.5.4 Delete or Modify Substructures Delete Substructures

Menubar: Icon:

Select the substructure(s) to be deleted, then Edit > Delete > Selected or Selected Atoms Click on the Edit toolbar to delete the current selection.

Command Line:

REMOVE SUBSTRUCTURE expression

•

expression—Substructure expression indicating substructure(s) to delete.

Modify Substructures Substructure modification is not accessible from the menubar. Modify a Substructure’s Name: MODIFY SUBSTRUCTURE NAME substructure_expr {mode name}

•

substructure_expr—Substructures to modify.

•

mode: APPEND_AUTO—Single string is supplied and concatenated with selected

substructure’s current name. QUERY—Name for each selected substructure is entered. Each selected substructure is highlighted as you are prompted for its name. SEQUENTIAL_AUTO—Element type name is concatenated with substructure ID number. •

name—Name or fragment thereof to associate with the substructure in all but SEQUENTIAL_AUTO mode. First character must be alphabetic and may contain alphabetic, numeric, and the apostrophe.

To rename substructures (residues) in a biopolymer, use the BIOPOLYMER RENUMBER command. Modify a Substructure’s Root Atom: MODIFY SUBSTRUCTURE ROOT substructure_expr {atom_sel}

•


•

atom_sel—Atom to be the root of each of the selected substructures.

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Substructures are composed of connected atoms forming a “graph” structure. The graph is traversed from the “root” to all other atoms in the substructure. All bonds within the substructures are ordered such that when traversed from origin to terminus, they are directed away from the root. The original root is selected arbitrarily by the program. This command alters the root of the substructure and re-orders the graph. Modify a Substructure’s Type: MODIFY SUBSTRUCTURE TYPE substructure_expr {type}

•


•

type—DOMAIN, GROUP, PERMANENT, RESIDUE, TEMPORARY.

All types that are not temporary are permanent. Only RESIDUE has any special meaning. It is used extensively in the manipulation of biopolymers where it is synonymous with monomer. Generally you should not alter the substructure types; they are managed by the system. Create/Modify a Substructure’s Comment: MODIFY SUBSTRUCTURE COMMENT substructure_expr {comment}

•


•

comment—Descriptive string. It may contain any characters and be of arbitrary length. Use double quotes when entering spaces or special characters via command line.

8.5.5 Chirality Determine Chirality Menubar: Command Line:

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Edit > Chirality > Find • CHIRAL PRO_RS atom_expr—Determine PRO-R or PRO-S chirality of the specified atoms. • CHIRAL RS atom_expr—Determine R or S chirality of the specified atoms. • CHIRAL ZE bond_expr—Determine Z or E isomerism about the specified double bonds. • CHIRAL MARK_RS atom_expr—Determine R or S chirality of the specified atoms and set the atom chirality attribute. • CHIRAL MARK_ZE bond_expr—Determine Z or E isomerism about the specified double bonds and set the bond stereo attribute.

SYBYL-X 1.1


Both the chirality of an atom and the cis-trans isomerism about a double bond can be determined by using a set of rules developed by Cahn, Ingold and Prelog and adopted by IUPAC (See J. Org. Chem., 35, 9, 2849, (1970)). These rules govern the sequencing of substituents about the chiral atom or double bond. Once the substituents are assigned a priority, simple geometric algorithms determine which type of isomerism is present. These same rules are used to determine the prochirality of an atom. The system determines the RS isomerism of an atom by positioning a threedimensional representation of the atom so that the lowest group in the sequence is oriented away from the viewer. If the remaining substituents are arranged in a clockwise manner by priority, the center is designated R, otherwise it is S. ZE isomerism about a double bond is a more general designation than cis-trans; it is determined by examining the bond’s substituents and sequencing them in the manner prescribed by IUPAC (atomic number is the first criterion) which encompasses the Cahn/Ingold/Prelog sequencing rules. The special relationship between the higher priority substituent on each end of the double bond is examined relative to a reference plane, which includes the two double bonded atoms, and drawn perpendicular to the plane of the four substituents. If the two higher priority substituents lie on the same side of this reference plane, the isomerism is denoted as Z; if they lie on opposite side, it is E. Atom chirality attributes are used by the expression generator %sln() when converting a SYBYL molecule to an SLN string. The chirality will then be expressed as [S=N] or [S=I] (see the SLN Manual for details). The bond stereo attributes are also used by the expression generator %sln(). Any unfilled valences are assumed to be occupied by hydrogens. The built-in set {CHIRAL} determines only RS isomerism. Additional Information: •

TAILOR SET CHIRAL to alter the method for calculating chirality.

Invert Chirality Menubar: Command Line:

Edit > Chirality > Invert INVERT atom_expr

If all atoms in the molecule are to be inverted, the entire molecule is inverted by reflecting the X-coordinate through the YZ plane. Otherwise, each individual tetrahedral atom is inverted by exchanging two substituents. Note that nonchiral centers may also be inverted.

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Atoms at ring fusions cannot be inverted individually, but only as part of the inversion of the whole molecule. No chirality determination is done before or after the inversion. A message is issued only if a selected center cannot be inverted due to a ring fusion. A count of the number of tetrahedral centers successfully inverted is given. If a molecule includes atom chirality attributes, these attributes are inverted as well as the coordinates of the chosen atoms. Atom chirality attributes are set either by the CHIRAL_MARK_RS command or by using the expression generator %sln_to_mol() to convert an SLN string to a SYBYL molecule. Reflect Atoms Through a Plane Menubar: Command Line:

Edit > Chirality > Reflect through Plane REFLECT atom_expr plane_name

• •

atom_expr—Atoms to reflect through the plane. plane_name—Name of plane through which reflection is done.

The plane must be defined on the molecule. Any arbitrary atoms may be reflected through the plane. Examine the resulting bonding geometry carefully, since the program pays no attention to the geometrical arrangement during this operation. Additional Information: •

DEFINE PLANE to calculate the equation of the plane.

Delete Stereo Atom Attribute from a Molecule Description Delete the stereo atom attributes. Menubar: Command Line:

Not accessible from the menubar. REMOVE STEREO_ATOM_ATTR expression

Delete Stereo Bond Attribute from a Molecule Description Delete the stereo bond attributes. Menubar: Command Line:

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Not accessible from the menubar. REMOVE STEREO_BOND_ATTR expression

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8.5.6 Center of Rotation, Name, Type, etc. of a Molecule Change Center of Rotation via Command Line:

MODIFY MOLECULE CENTER_OF_ROTATION mol_area atom_sel

• mol_area—Molecule area containing molecule. • atom_sel—Atom(s) to use as center of rotation. Or CENTER atom_expr

Computes the average X, Y and Z for the specified group of atoms and translates the molecule so that this position becomes the origin of the molecule coordinate system. Reset will restore the original coordinates. For more information see CENTER (in the Graphics Manual). To save the new coordinates, use FREEZE in the Graphics Manual). To simply view the molecule in the center of the screen without affecting its coordinates use CENTERVIEW (in the Graphics Manual). Create/Modify Comment via Command Line:

Create/Modify Name via Menubar:

Create/Modify Name via Command Line:

SYBYL-X 1.1

MODIFY MOLECULE COMMENT area {comment}

• •

area—Area(s) containing molecule(s) to modify. comment—Descriptive string, may contain any characters and be of arbitrary length. Use double quotes when entering spaces or special characters via command line. Edit > Molecule > Name • At least one atom must have been pre-selected. • If atoms were selected in multiple molecule areas you will be prompted to specify which molecule area contains the molecule to be named. MODIFY MOLECULE NAME area {name}

• •

area—Area(s) containing molecule(s) to modify. name—Name to identify molecule and key for its storage and access in database. If molecules are saved into a SYBYL Mol2 database, filenames are generated from molecule names. For database use, avoid names containing: colon (:), question (?), backslash (\), and space ( ). If the file and molecule name are to be manipulated in SPL, avoid: circumflex (^) and pipe (|). Names are required before adding a molecule to a database (see Add Molecule(s) to a Database on page 174).

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Change Root via Command Line:

MODIFY MOLECULE ROOT mol_area {substructure_sel comment}

•

mol_area—Area(s) containing molecule(s) to modify. • substructure_sel—Substructure to be the root of the molecule tree. • comment—Comment to store with new root. Molecules may have any number of independent connected fragments, each one composed of at least a single substructure. Each fragment has one of its substructures recorded in the molecule header, i.e., the “root” of the fragment “tree”. Change Type via Command Line

MODIFY MOLECULE TYPE mol_area {type}

• •

mol_area—Area(s) containing molecule(s) to modify. type—NUCLEIC_ACID_MOLECULE, SACCHARIDE_MOLECULE, PROTEIN, SMALL_MOLECULE, MACRO_MOLECULE.

8.5.7 Combine (Fuse) Two Molecules Menubar: Command Line:

Not accessible from the menubar. FUSE {atom_pairs}

The two structures do not have to be cyclic. At least two atoms must be selected in each molecule; more atoms help direct fusion of non planar bonds. Terminate the input list with the end-loop character (|). SYBYL places the fused structure in the molecule area of the first atom of each pair. Coordinates of atoms used for the fusion are taken from the first molecule. The bonds directly connecting fusion atoms in each molecule are discarded. An attempt is made to retain all other bonds in both molecules. If the atomic valence of the fusion atom is exceeded, any Hs attached to fusing atoms are discarded and the fusion rechecked. If the operation still fails, an error is reported and the command terminated. You must then discard enough atoms to make fusion legal. If the operation succeeds, Hs are replaced to fill valences of atoms from which they were removed. If you specify fusion of two molecules across an aromatic or double bond by selecting only two atoms, alignment of resulting fragments is unambiguous. If, however, fusion across a single bond involving tetrahedral atoms is specified by two atoms, ambiguity arises. The program attempts to select the alternative which results in the best fusion geometry. If you prefer another alternative fusion geometry, select three or more atoms to unambiguously establish the geometry.

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Spiro fusions cannot be specified by selecting a single atom pair. They can be specified by adding Hs and indicating the fusion of an internal bond in one molecule with the bond involving the H atom. Additional Information: •

Ring Fusion Tutorial on page 103.

•

TAILOR SET FUSE to select default parameter set to alter character-

istics of the fusion.

8.5.8 Combine (Join) Two Molecules Menubar: Command Line:

Not accessible from the menubar. JOIN target_atom new_group_atom

• •

target_atom—Atom to replace with group being added. new_group_atom—Atom in joining group being discarded when group is fused to molecule.

This functionality cannot be used to form a ring closure bond. The length of the new bond is determined by the type of the atoms being joined and is taken from a table of standard bond lengths. The two atoms specified are eliminated by the join operation. Groups being joined may be in same molecule area or in different areas. In the latter case, atoms to be joined are copied into the target atom’s molecule area and then the bond formed. Additional Information: •

Add Bonds Manually on page 125 to connect two atoms.

•

Merge Molecule Areas on page 56.

•

TAILOR SET JOIN to customize the parameters for joining.

8.5.9 Adjust Bond Lengths and Angles to Match Standards The Shaked algorithm iteratively loops through the selected atoms, adjusting bond lengths and bond angles, to more closely match standard values stored in the bond length and the Tripos force field bond angle tables. Corrections are applied to coordinates to satisfy distance constraints: L ij ≤ D ij ≤ U ij

SYBYL-X 1.1

[EQ 2]

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135


Where Lij is the lower bound for the distance (Dij) between atoms i and j, and Uij is the upper bound. A delta of 0.05 is added to or subtracted from the value obtained from the parameter tables to derive the upper and lower bounds, respectively. This operation is performed until either the maximum number of iterations (100) is reached or convergence has occurred, that is, all constraints are met. The algorithm fails when distance constraints are inconsistent or the input structure is very different from the structure that obeys all distant constraints. This algorithm is described by I. Haneef, Simon J. Talbot, and Peter G. Stockley in J. Mol. Graphics, 7, 186-195 (1989). Menubar:

Edit > Clean-Up Molecule > Shake Bonds and Angles Acts on selected atoms in a single molecule area.

Command Line:

SHAKED atom_expr

8.5.10 Scan Torsions to Reduce van der Waals Contacts Menubar:

Edit > Clean-up Molecule > Scan Torsions Acts on selected bonds in a single molecule area.

Command Line:

SCAN bond_expr

The specified torsion angles are scanned, through a full 360°, for positions which relieve bad steric interactions. Only one bond at a time is altered. After a position is found, that bond is removed from the set being considered. Scanning continues until all interactions dependent upon these bonds are relieved or until no progress is made from one iteration to the next. Interrupt the process by typing C. Additional Information: •

TAILOR SET SCAN to alter characteristics of the scan.

•

The following BIOPOLYMER subcommands: ADD_SIDECHAIN, CHANGE, INSERT, JOIN, SET CONFORMATION.

8.5.11 Create a Molecule by Averaging Existing Molecules AVERAGE_MOL mol_expr mol_area mol_expr

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Expression indicating location of existing molecules. Empty molecule areas are ignored.

SYBYL-X 1.1


mol_area

Area in which to place new molecule. Default is lowest numbered empty molecule area.

Assuming the starting set of molecules are different conformations of the same structure, this command creates another conformation (of the same molecule) where: •

Coordinates of every atom are the average of the X, Y, Z coordinates of corresponding atoms in selected molecules.

•

All other aspects of the molecule (bonds, substructures, features, etc.) are taken (arbitrarily) from one of the selected molecules.

If the selected molecules do not all contain the same number of atoms, an error message is displayed and no molecule is created. Make sure all other aspects of the molecules are consistent (bonds, substructures, etc.).

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Chapter 8. Build and Modify Molecules Define and Modify Geometric Features

8.6 Define and Modify Geometric Features •

Center of Mass on page 138

•

Centroid on page 139

•

Extension Point on page 140

•

Line on page 141

•

Normal to a Plane on page 142

•

Plane on page 143

•

Renumber Atoms on page 144

•

UNITY Query Features on page 145

Note: Whole or partial re-orientation (via Fit Atoms, Freeze Molecule, ORIENT, geometrical modification or manipulation of rotatable bonds) after defining centers of mass, centroids, extension points, normals, or planes renders the feature invalid. Use the EVALUATE command to update the feature’s position. Additional Information: •

VISUALIZE, in the Graphics Manual, to display some of the defined

features. •

List Information About SYBYL Objects on page 155.

8.6.1 Center of Mass A centroid is a dummy atom at the center of a group of atoms. The center of mass is a centroid with coordinates weighted by the atomic masses. When defined, the dummy atom is added to the coordinate list and a feature in the molecular description. The dummy atom is connected through a dummy bond to the atom used in the calculation closest to its position. Dummy atoms have the type Du and are colored magenta. Note: Atomic weights now (SYBYL 7.1) correlate with the latest accepted figures from IUPAC and NIST. The average difference is 0.01% of the values in SYBYL 7.0. For unstable atoms, the values for the most stable isotope are used. •

IUPAC: Pure Appl. Chem., Vol.75, No.8, pp 1107-1122, 2003.

•

National Institutes of Standards and Technology (NIST)

For more information, see $TA_ROOT/sybylbase/tables/metals/ATOM_DEF

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Define Re-Evaluate:

DEFINE CENTER_OF_MASS atoms center_name comment EVALUATE CENTER_OF_MASS mol_area name

•

mol_area—Area(s) containing center(s) of mass to evaluate. • name—Name of center(s) of mass to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). The new coordinates are computed and stored in the molecular definition. In addition, dummy atoms representing the position of the features are adjusted to reflect the new values. Remove

REMOVE CENTER_OF_MASS mol_area name

• •

mol_area—Area(s) containing center(s) of mass to delete. name—Name of center(s) of mass to delete.

8.6.2 Centroid A centroid is a dummy atom at the center of a group of atoms. When defined, it is added to the coordinate list and a feature in the molecular description. The dummy atom is connected through a dummy bond to the atom used in the calculation closest to its position. Dummy atoms have the type Du and are colored magenta. (See TAILOR SET CENTROID to alter the characteristics of the centroid.) Define via the Menubar: Define via Command Line: Re-Evaluate:

Edit > Centroid > Define DEFINE CENTROID atom_expr centroid_name comment EVALUATE CENTROID mol_area name

• •

Remove via the Menubar:

SYBYL-X 1.1

mol_area—Area(s) containing centroid(s) to evaluate. name—Name of centroid(s) to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). The new coordinates are computed and stored in the molecular definition. In addition, dummy atoms representing the position of the features are adjusted to reflect the new values. Edit > Centroid > Delete

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Remove via Command Line:

REMOVE CENTROID mol_area name

• mol_area—Area(s) containing centroid(s) to delete. • name—Name of centroid(s) to delete. Any features (plane, normal, constraint) attached to that centroid are removed as well.

8.6.3 Extension Point An extension point is a dummy atom connected to the molecule that can be used as a place holder. The extension point can represent a ligand atom or a hydrogen bond partner. It is added as a dummy atom in the coordinate list and a feature in the molecular description. It is connected through a dummy bond to atom1. Define

DEFINE EXTENSION_POINT atom1 atom2 atom3 dist ang tors name comment

•

• • • • • Re-Evaluate:

atom1, atom2, atom3—IDs of atoms defining extension point. If any are lone pairs, use the command MODIFY ATOM LONE_PAIR first. dist—Distance of extension point to atom1. ang—Angle for extension point, atom1, and atom2. tors—Torsion angle for extension point, atom1, atom2, and atom3. name—Name for extension point. comment—Arbitrary string associated with the extension point.

EVALUATE EXTENSION_POINT mol_area name

• •

mol_area—Area(s) containing point(s) to evaluate. name—Name of point(s) to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). The new coordinates are computed and stored in the molecular definition. In addition, dummy atoms representing the position of the features are adjusted to reflect the new values. Remove

REMOVE EXTENSION_POINT mol_area name

• •

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mol_area—Area(s) containing point(s) to delete. name—Name of point(s) to delete.

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8.6.4 Line A line adds a dummy atom at a specified distance along the path between two atoms. Define

DEFINE LINE origin_atom positive_atom dist name comment

• • •

• • Re-Evaluate:

origin_atom—Atom defining origin of line. positive_atom—Atom defining direction of line from origin_atom. dist—Distance (Å) from origin_atom to dummy atom. Positive value indicates “towards” positive_atom, a negative value corresponds to “away from.” name—Name for line. comment—Arbitrary string associated with line and dummy atom.

EVALUATE LINE mol_area name

• •

mol_area—Area(s) containing line(s) to evaluate. name—Name of line(s) to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). The new coordinates are computed and stored in the molecular definition. In addition, dummy atoms representing the position of the features are adjusted to reflect the new values.

Remove

REMOVE LINE mol_area name

• •

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mol_area—Area(s) containing line(s) to delete. name—Name of line(s) to delete.

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8.6.5 Normal to a Plane A normal is a line normal to an existing plane through an atom.The normal is represented by two dummy atoms on either side of a specified atom. Two dummy bonds connect them to the midpoint. The bonds are perpendicular to the specified plane. Distance from the midpoint to the dummy atoms is a variable set at 1 Å by default. The normal is stored as two dummy atoms, two dummy bonds and a feature in the molecular description. Dummy atoms have the type Du and are colored magenta. Define via the Menubar: Define via Command Line:

Edit > Normal > Define DEFINE NORMAL atom_sel plane_name normal_name comment

The two dummy atoms are named “normal_name” followed by 1 or 2. Re-Evaluate:

EVALUATE NORMAL mol_area name

• •

Remove via the Menubar: Remove via Command Line:

mol_area—Area(s) containing normal(s) to evaluate. name—Name of normal(s) to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). Plane coordinates and plane normal lines are not updated after whole or partial re-orientation of the molecule (via Fit Atoms, Freeze Molecule, ORIENT, geometrical modification or manipulation of rotatable bonds). Use the EVALUATE PLANE command first then re-evaluate the normal line(s). Edit > Normal > Delete REMOVE NORMAL mol_area name

• mol_area—Area(s) containing normal(s) to delete. • name—Name of normal(s) to delete. Any features (e.g., constraints) attached to that normal are removed as well. If an atom, real or artificial, and involved in a normal definition, is removed, the normal is removed automatically.


142

•

See Plane on page 143 for information about how to define the required plane.

•

See TAILOR SET NORMAL to alter the characteristics of the normal.

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8.6.6 Plane A plane is represented by four dummy atoms connected by four dummy bonds delineating a parallelogram. (See TAILOR SET PLANE to alter the characteristics of the plane.) The plane is stored as four dummy atoms, four dummy bonds and a feature in the molecular description.Dummy atoms have the type Du and are colored magenta. Edit > Plane > Define

Define via the Menubar: Define via Command Line:

•

Re-Evaluate:

EVALUATE PLANE mol_area name

DEFINE PLANE atom_expr plane_name comment

atom_expr—The atoms to use in calculating the plane equation: from a minimum of 3 non-linear atoms up to all the atoms in the molecule. • plane_name—Name to give to the new plane • comment—An arbitrary string associated with the plane The four dummy atoms are named “plane_name” followed by 1, 2, 3, or 4. The equation of the least squares plane is printed in the console along with the RMS distance of the defining atoms to the plane. • •


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mol_area—Area(s) containing plane(s) to evaluate. name—Name of plane(s) to evaluate. Enter a question mark (?) to list names. Expression may include the wildcard character (*) (e.g., to remove both c1 and c2, enter c*, but the expression c1,c2 is not valid). Use this feature to update the plane equation and dummy atom coordinates after whole or partial re-orientation of the molecule (via Fit Atoms, Freeze Molecule, ORIENT, geometrical modification or manipulation of rotatable bonds). Lines normal to a plane, if present, must be reevaluated via the EVALUATE NORMAL command. Edit > Plane > Delete REMOVE PLANE mol_area name

• mol_area—Area(s) containing plane(s) to delete. • name—Name of plane(s) to delete. Any features (e.g., constraints) attached to that plane are deleted along with the plane. If an atom, real or artificial, and involved in a plane definition, is removed, the plane is removed automatically.

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Normal to a Plane on page 142 for using a plane to define a normal.

•

Reflect Atoms Through a Plane on page 132

8.6.7 Renumber Atoms Renumbering atoms imposes an arbitrary order on atoms in a molecule for the purposes of Z-matrix formation. It is done prior to submitting the molecule to quantum mechanical calculations. Menubar: Command Line:

Not accessible from the menubar. RENUMBER origin_area target_area {atom_sel}

• • •

origin_area—Area containing molecule to renumber. target_area—Area to receive renumbered molecule. atom_sel—Atoms to renumber, in the new numerical order.

Renumbering atoms causes all defined features to be deleted from the molecule because there is no automatic translation from the internal representation of the feature definition to atom numbers. All other information about the molecule is suitably transformed and restored after renumbering. You are prompted for the ID number of the atom you want in each position. (To display current atom numbers, use LABEL ID * before renumbering.) Positions are given in sequence from 1 to the number of atoms in the molecule. Specification can be terminated at any time. Atoms not specified to be renumbered retain their relative order and are added to the molecule list immediately behind atoms which were renumbered.

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8.6.8 UNITY Query Features A UNITY geometrical feature or constraint for a structure is used within a UNITY database query. UNITY features are displayed as background objects and can be saved as part of the molecular definition. The TAILOR SET UNITY command can be used to select the color for highlighting constraints, features, and receptor sites. For details on defining specific features and constraints, see the “UNITY Queries” chapter, in the UNITY Manual. Define via the Menubar: Define via Command Line:

UNITY > Edit Query > Add Features DEFINE UNITY_FEATURE option

• • • • • • • • • • • •

Delete NonQuery Atoms via the Menubar:

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4_POINT_ANGLE_CONSTR AINT ACCEPTOR_ATOM ACCEPTOR_SITE ANGLE_CONSTRAINT AROMATIC BOND_PATH CENTROID

•

• • • •

• • • CONTAINING_VOLUME_CO • NSTRAINT • DISTANCE_CONSTRAINT • DONOR_ATOM •

LINE LP_ANGLE_CONSTRAINT NEGATIVE_CENTER NORMAL_POINT PARTIAL_MATCH_CONSTR AINT PLANE POSITIVE_N RECEPTOR_SITE SPATIAL_CAP SPATIAL_LINE SPATIAL_PLANE SPATIAL_POINT

DONOR_SITE EXCLUDED_VOLUME_CONS TRAINT EXTENSION_POINT FRAGMENT HYDROPHOBIC

• • • •

STERIC_FEATURE SURFACE_VOLUME TETRAHEDRAL TORUS

• • • UNITY > Edit Query > Delete > Atoms not in the Query The list of atoms to remove is displayed in the atom expression dialog and highlighted on the molecule. Changes to the atom expression may be made before pressing OK to remove the atoms.

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Delete NonQuery Atoms via Command Line:

Modify via the Menubar: Modify via Command Line:

REMOVE NON_QUERY_ATOMS mol_area

• mol_area—Area containing the UNITY query. A list of atoms to remove is displayed in the atom expression dialog and highlighted in the molecule. Changes to the atom expression may be made before pressing OK to remove the atoms. If the molecule area does not contain any UNITY features or constraints, no action is taken. UNITY > Edit Query > Manage Features MODIFY UNITY_FEATURE mol_area feature/constraint [{attribute value}] [COLOR]

•


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mol_area—Molecule area containing feature or constraint. • feature/constraint—Feature or constraint to modify. • attribute—Name of an attribute. Modifiable attributes are type-specific, and depend on feature or constraint selected. • value—Value for the attribute. • COLOR—Optional for UNITY features only. UNITY > Edit Query > Delete > Features UNITY > Edit Query > Manage Features REMOVE UNITY_FEATURE mol_area name

• •

mol_area—Area containing feature or constraint. name—Name of UNITY feature or constraint to delete. Type ALL instead of a single name to delete all features and constraints. Any constraints based on that feature are removed as well. If an atom, real or artificial, and involved in a feature or constraint definition, is removed, the feature or constraint is removed automatically.

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Chapter 9.

Geometric Measurements •

Intra-/Intermolecular Measurements on page 148

•

List Coordinates, Distances, or Angles on page 149

•

Measure the Intramolecular Angle Between Planes on page 150

•

Measurements Specific to UNITY Features on page 151


BIOPOLYMER MEASURE to measure omega and zeta angles.

•

TAILOR SET GENERAL ANGLE_RANGE to specify how an angle range

should be displayed.

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Chapter 9. Geometric Measurements Intra-/Intermolecular Measurements

9.1 Intra-/Intermolecular Measurements Angles Menubar: Command Line:

Compute > Measure > Angle MEASURE ANGLE {atom1 atom2 atom3}

Loops until you type the end-loop character (|). UIMS2 Variable:

MEASURE_ANGLE

Distance Menubar: Command Line:

Compute > Measure > Distance MEASURE DISTANCE {atom1 atom2}


MEASURE_DISTANCE

Height of Atoms Above Plane Menubar: Command Line:

Compute > Measure > Height Above Plane MEASURE HEIGHT atom_expr plane_name

• •

atom_expr—Atoms whose height is to be measured. plane_name—Name of plane, in default work area, to use. Use LIST PLANE to find names of defined planes. Note: Plane coordinates and plane normal lines are not updated when you use FREEZE. Use EVALUATE PLANE mol_area name, then EVALUATE NORMAL mol_area name to update the plane and normal line. UIMS2 Variable:

MEASURE_HEIGHT

Torsion Angles Menubar: Command Line:

Compute > Measure > Torsion MEASURE TORSION {atom1 atom2 atom3 atom4}


MEASURE_TORSION


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List Coordinates, Distances, or Angles on page 149.

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Chapter 9. Geometric Measurements List Coordinates, Distances, or Angles

9.2 List Coordinates, Distances, or Angles Menubar: List Bond Angles via Command Line:

Compute > Measure > Topography

List Bond Lengths via Command Line:

TOPOGRAPHY BOND_LENGTH atom_expr

List Coordinates via Command Line:

TOPOGRAPHY COORDINATES atom_expr

TOPOGRAPHY ANGLES atom_expr

•

•

atom_expr—Expression indicating angle(s). All angles having the center atom in this atom expression are listed atom_expr—Expression indicating bond(s). All bonds having either their origin or their target in this expression are listed.

•

atom_expr—Expression indicating atoms whose coordinates are to be listed. Coordinates listed by this command are affected by rotations and translations applied to molecule on the terminal. To list coordinates in memory, use the LIST ATOMS command. Alternatively, cancel rotation/translation matrix using the reset feature on your terminal, or FREEZE coordinates before issuing the TOPOGRAPHY command.

List Non-bonded Distance via Command Line:

TOPOGRAPHY NON_BONDED_LENGTH atom_expr1 atom_expr2

List Torsion Angles via Command Line:

TOPOGRAPHY TORSION_ANGLE bond_expr

Distances between every atom in atom_expr1 and every atom in atom_expr2 are listed. •

bond_expr—Expression indicating torsion(s). All torsion angles having the center bond in this bond expression are listed.


Record the Output from a Single Command on page 194.

•

Intra-/Intermolecular Measurements on page 148.

•

BIOPOLYMER MEASURE to conveniently measure omega and zeta angles.

•

BIOPOLYMER CHECK_GEOMETRY to report deviations from standard

geometry.

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Chapter 9. Geometric Measurements Measure the Intramolecular Angle Between Planes

9.3 Measure the Intramolecular Angle Between Planes Menubar: Command Line:

Compute > Measure > Plane Angle MEASURE PLANE_ANGLE mol_area plane_name1 plane_name2 Use LIST PLANE to find names of defined planes.

Note: Plane coordinates and plane normal lines are not updated when you use FREEZE. Use EVALUATE PLANE mol_area name, then EVALUATE NORMAL mol_area name to update the plane and normal line. UIMS2 Variable:

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MEASURE_PLANE_ANGLE

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Chapter 9. Geometric Measurements Measurements Specific to UNITY Features

9.4 Measurements Specific to UNITY Features MEASURE UNITY_MEASUREMENTS mol_area option Option: ANGLE atom1 atom2 atom3 DISTANCE atom1, atom2 HEIGHT atom_expr plane_name PLANE_ANGLE plane_name1 plane_name2 TORSION atom1 atom2 atom3 atom4

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Measure angle of atoms. Measure distance between atoms. Measure height of atom above plane. Measure angle between planes in same work area. Measure torsion angle of atoms.

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Chapter 10.

Get Information on SYBYL Objects •

Information on Selected Objects on page 154 •

Right-Click for Information on page 154

•

Atoms, Bonds, or Substructures on page 154

•

List Information About SYBYL Objects on page 155

•

Print Information About SYBYL Objects on page 156

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Chapter 10. Get Information on SYBYL Objects Information on Selected Objects

10.1 Information on Selected Objects 10.1.1 Right-Click for Information Atom right-click > Molecule Properties A dialog displays the name of the molecule and the computed values of several physical and chemical properties. Atom right-click > Atom Properties A dialog displays the atom’s name and that of the molecule it belongs to as well as several computed properties.

10.1.2 Atoms, Bonds, or Substructures Report information about the selected object in the console. Menubar:

Options > Info • Atom then click the atom(s) of interest • Bond then click two bonded atoms • Substructure then click any atom in the substructure (residue) of interest. Press End to terminate the information loop.

Command Line:

INFORMATION object_type object_sel • object_type—ATOMS, BONDS, SUBSTRUCTURES.

•

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object_sel—ID for individual object. Prompting continues until you enter the end-loop character (|).

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Chapter 10. Get Information on SYBYL Objects List Information About SYBYL Objects

10.2 List Information About SYBYL Objects Menubar: Command Line:

Options > List LIST object_type object_expr [mode] • object_type—AGGREGATES, ATOMS, BACKGROUNDS, BONDS, BUILT_IN_SETS, CENTER_OF_MASS, CENTROID, CONSTRAINT, EXTENSION_POINT, GLOBAL_SETS, LINE, LOCAL_SETS, MOLECULES, NORMAL, PLANE, SEQUENCE, SUBSTRUCTURES, TABLE, TAILOR, UNITY_FEATURE, VIOLATIONS.

• •

object_expr—Particular set of objects of object_type to list. mode—BRIEF (one line summary for each object or FULL (all available information for each object) for most objects. ALL, TYPE, or NAME for UNITY features. (In picking mode, NAME allows picking on the screen of a particular feature.)

In the atom, bond, and substructure list, an asterisk (*) in the column following the ID indicates that the object belongs to an internal ring (i.e., a ring totally contained within a substructure), whereas an “at” sign (@) indicates an external ring (i.e., a ring which spans substructure boundaries). Substructures cannot participate in internal rings but they can be members of external rings. For sets, an asterisk (*) in the column after the ID indicates that the set is defined and managed by the system. Additional Information: •

Record the Output from a Single Command on page 194 to copy the listing into a file.

•

Define and Modify Geometric Features on page 138.

•

TAILOR SET GENERAL ATOM_IDENTIFIER to alter the characteristics

of atom listings.

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Chapter 10. Get Information on SYBYL Objects Print Information About SYBYL Objects

10.3 Print Information About SYBYL Objects PRINT object_type object_expr [mode] object_type

object_expr mode

Type of object to include in the output: AGGREGATES, ATOMS, BACKGROUNDS, BONDS, BUILT_IN_SETS, CENTER_OF_MASS, CENTROID, CONSTRAINT, EXTENSION_POINT, GLOBAL_SETS, LINE, LOCAL_SETS, MOLECULES, NORMAL, PLANE, SEQUENCE, SUBSTRUCTURES, TABLE, TAILOR, VIOLATIONS. Objects to include in the output. Listing mode to use (BRIEF or FULL). This argument does not apply to all objects.

Use the full generality of the object expression syntax to determine which objects to include. The PRINT command writes out the file SYBYLPRINT.LIS and submits it to lpr for printing. In the atom, bond, and substructure list, an asterisk (*) in the column following the ID indicates that the object belongs to an internal ring (that is, a ring totally contained within a substructure), whereas an “at” sign (@) indicates an external ring (a ring which spans substructure boundaries). Substructures cannot participate in internal rings but they can be members of external rings. For sets, an asterisk (*) in the column after the ID indicates that the set is defined and managed by the system. Additional Information: •

TAILOR SET GENERAL ATOM_IDENTIFIER to alter the characteristics

of the listings.

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Chapter 11.

Use Molecule Databases •

Database Formats on page 158

•

Database Tutorial on page 159

•

Open and Close SYBYL Databases on page 166

•

Retrieve Molecules from a SYBYL Database on page 169

•

Obtain Information on Databases on page 173

•

Manage Database Content on page 174

•

Save Database Molecules to Mol2 Files on page 178

•

The DATABASE Command on page 180

•

Database Qualifiers on page 179

•

System Utilities on page 181

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Chapter 11. Use Molecule Databases Database Formats

11.1 Database Formats There are currently two different formats for molecule databases: •

mol2dbms—A directory of Mol2 files, containing individual molecules, and several other utility ASCII files. Often referred to as a Mol2 database. The directory name identifies the database. This format was introduced in SYBYL 6.1.

•

mdbms—A single file, binary format, introduced in SYBYL 5.x.

Note: To explore chemical and biological databases use UNITY, the search and analysis system. See the UNITY Manual. Because Mol2 databases are composed of only ASCII files, they are more portable across different machine platforms than binary databases (e.g., Mol2 databases are portable across platforms, whereas binary databases are not). Mol2 databases are less susceptible to corruption than binary databases and are more recoverable in case of corruption, since molecules can be held in separate files. However, manipulating files within a Mol2 database via the system shell while the database is open can generate error messages. Closing the database (and any tables using the database) and reopening it usually eliminates such errors. You can create a Mol2 database using the DATABASE CREATE and DATABASE XCREATE commands, or from the system shell using existing Mol2 files created by other parts of SYBYL. For example, see the Database Tutorial on page 159. Also see the TAILOR SET DATABASE command for information about the MULTIMOL2 variable and how it affects Mol2 databases created from the system shell.

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Chapter 11. Use Molecule Databases Database Tutorial

11.2 Database Tutorial This tutorial describes some of the capabilities developed for the manipulation of molecule databases. This tutorial demonstrates: •

Adding new molecules to a database.

•

Defining sets of molecules in the database. Note: Definition of database sets is only possible via the DATABASE command.

•

Defining relations on these sets.

•

Several access methods for looking at the contents of a database.



¾ ¾



2. Copy a file from the demo directory to your working directory.

¾

cmd cp -r $TA_DEMO/aa.mdb . (include the space and period)

11.2.2 Open the Database 1. Open the database of amino acids and examine its contents.

¾ ¾ ¾

File > Database > Open Select aa.mdb and press OK. Select UPDATE and press OK.

The console reports that the database is open and in UPDATE mode. Databases can be opened in UPDATE or READONLY mode. If opened in READONLY mode, any number of users may simultaneously access the database. On the other hand, no changes can be made to a database unless it is opened in UPDATE mode. 2. Display a list of the molecules in the amino acid database.

¾

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File > Database > List

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¾ ¾

Select MOLECULE and press OK. Accept * as the Object Name and press OK.

SYBYL displays the names in the console.

11.2.3 Define (Static) Sets of Molecules 1. Enter the DATABASE mode.

¾

In the console, type: MODE DATABASE

Note: The prompt in the console changes to Database command>. Tip: Use the MODE command for complex commands which have many options. It allows you to establish the upper level command and only enter options until you exit this mode. When you are in this mode, any command not available as an option can be invoked by preceding it with the word COMMAND. 2. Organize the polar amino acids, according to their charge, into sets named basic, acidic, and polar_neutral. Include a comment string describing the set.

¾

Type the following. Important: Do not introduce spaces in the list of amino acids for the Query Expressions.

Database command> DEFINE SET basic Query Expression lysine,arginine,histidine Comment String Amino acids with positively charged R groups Database command> DEFINE SET acidic Query Expression *acid Comment String Amino acids with negatively charged R groups Database command> DEFINE SET polar_neutral Query Expression glycine,serine,threonine,cysteine,tyrosine,asparagine,glutamine Comment String Polar amino acids with uncharged R groups

Database sets are user-defined groups of molecules which have some shared property (or properties). These properties are distinguished from the ones which Tripos defines (molecule types,…) and database classes. The group membership of database sets is static.

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3. Examine the contents of the newly created sets.

¾

SHOW SET *

The definitions of all sets in the current database are shown in the console. There is no limit on the number of sets.

11.2.4 Define (Dynamic) Classes of Molecules 1. Define two database classes by specifying rules that identify groups of molecules as hydrophilic or hydrophobic.

¾

Type the following:

Database command> DEFINE CLASS hydrophilic Query Expression basic+acidic+polar_neutral Comment String Polar amino acids Database command> DEFINE CLASS hydrophobic Query Expression ~hydrophilic Comment String Nonpolar amino acids

Important: Database classes are defined by a formula, such as (basic+acidic+polar_neutral), which is stored as the definition of the group. Whenever the membership is to be evaluated, it reflects the contents of the database at that time—not at the moment when the definition was made. In this way they become dynamic, adapting their contents to the database as it changes. 2. Examine the contents of the classes.

¾

Type: SHOW CLASS *

The definition and contents of all classes in the database are displayed. Notice how HYDROPHOBIC contains everything that is not HYDROPHILIC (or more precisely, “not in the property group hydrophilic”). 3. Exit the DATABASE command mode.

¾

Type: ENDMODE


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Define/Modify Definitions of Groups on page 176

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11.2.5 Build a New Molecule Add hydroxyproline to the database. 1. Retrieve proline from the database to use as a template.

¾ ¾

File > Database > Get Molecule Select PROLINE and press OK.

2. Label the atoms.

¾

Use on the View toolbar to label the atoms by ID numbers (Atoms > Atom ID).

3. Add the hydroxyl group.

¾ ¾

In the console type: add group oh replace Click the hydrogen labeled 13.

11.2.6 Add the New Molecule to the Database Give the molecule its proper name and add it to the database. Molecule names may be any arbitrary string. 1. Name the new molecule

¾ ¾ ¾

Click on any atom then Edit > Molecule > Name In the Name Molecule dialog, enter hydroxyproline and press OK. Clear the selection.

2. Add hydroxyproline to the database.

¾

File > Database > Put Molecule

The console reports that hydroxyproline is added to the database.

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11.2.7 Redefine a Set and its Effect on the Class 1. Set the screen to quartered mode.

¾

Use on the Display toolbar to set the screen mode to Quartered.

2. Since hydroxyproline is an uncharged polar molecule, add it to the POLAR_NEUTRAL set.

¾

In the console, type the following:

MODE DATABASE Database command> DEFINE SET polar_neutral Query Expression polar_neutral+hydroxyproline

¾

Press the Enter key on your keyboard when prompted for a comment string.

Sets may be redefined at any time, even in terms of their own current contents, so that it is easy to add a new member. 3. Re-examine the classes.

¾

Type: SHOW CLASS *

Notice that hydroxyproline has been automatically added to the definition of HYDROPHILIC. Since the class “hydrophilic” was defined in terms of the groups “acidic”, “polar_neutral”, and “basic”, hydroxyproline automatically becomes a member of “hydrophilic”.

11.2.8 Search the Database The next few sections present different ways of accessing database molecules. The simplest way to retrieve is by molecule name. If you do not know the name, either at all or exactly, use a wildcard to search the database (by name) for any matching string. The wildcard (*) alone selects all of the molecules.

¾

Type: SEARCH NAME *

The console displays Select Command.

¾

Press the Enter key.

The console displays Query Expression

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1. Select leucine from the database.

¾

Type: leucine and press the Enter key.

The console displays Selected Molecule: LEUCINE

¾

In the Molecule Area dialog, select M2 and press OK.

Use the SELECT command with either the molecule’s full or partial name (with wildcards). 2. Retrieve histidine from the hydrophilic class. The DATABASE command can use property group definitions as a basis for generating selection menus. The Standard Fragment Library is organized using just this feature.

¾

Type: SEARCH MENU Hydrophilic NAME The following appears in the console: Hydrophilic 1. basic 2. acidic 3. polar_neutral

Menu items are selected by number. You may move down a level, back up a level, or go to the top.

¾

Type 1. Basic 1. ARGININE 2. HISTIDINE 3. LYSINE

¾ ¾

Type 2. Select M3 as the molecule area and press OK.

3. Use an expression to retrieve glutamic acid after first restricting your search to molecules that are both hydrophilic and acidic.

¾ ¾ ¾ ¾

164

Type: GET (hydrophilic&acidic) At the Selection Command prompt, press the Enter key. At Query Expression prompt, type: glu* Select M4 as the molecule area and press OK.

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You can use any combination of union, intersection, difference, and negation of property groups and name specifications (with or without wildcards) to select molecules for retrieval. These facilities, coupled with the ability to organize molecules into groupings meaningful to you, allow arbitrarily complex structures to be manipulated with ease.

11.2.9 Close the Database 1. Exit the DATABASE command mode.

¾

Type: ENDMODE

2. Close the database.

¾

File > Database > Close

3. This concludes the Database Tutorial.

¾

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Use

to reset the screen mode to Full.

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Chapter 11. Use Molecule Databases Open and Close SYBYL Databases

11.3 Open and Close SYBYL Databases •

Open a SYBYL Database on page 166

•

Create a New, Empty Database on page 167

•

Copy Database Contents to a New Database on page 168

•

Define a Database Alias on page 168

•

Specify the Default Database on page 168

•

Close a SYBYL Database on page 168

11.3.1 Open a SYBYL Database Notes about Databases: •

The database that is opened becomes the default user database.

•

If the database is already open, the access mode of the open database is changed to the newly specified mode.

•

Any number of users may have the same database open READONLY. However, if one user has a database open in APPEND or UPDATE mode, nobody else has any access to it until the database is closed. If one user has a database open in READONLY mode, nobody else is allowed to open it in APPEND or UPDATE mode.

•

SYBYL attempts to assign an alias to the newly opened database using the base name of the full database name. For example, if the full database name is /usr/me/mydb.mdb, SYBYL attempts to assign it the alias “mydb”. This makes using database qualifiers easier. See the ALIAS subcommand for more information about database aliases.


TAILOR SET DATABASE to alter characteristics of the database opening.

•

To unlock a database that was not properly closed because of a system crash, enter the following in a console: $TA_BIN/dbunlock

•

DATABASE OPEN assigns a value to the UIMS2 variable DATABASE_NAME.

Via the Menubar File > Database > Open The Database Selection dialog that is displayed is very similar to the dialog for opening files (see the Open File dialog description).

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Via the Command Line User Database:

DATABASE OPEN filename access_mode

• • System Database:

filename—Database to open (default extension is .mdb). access_mode—How database is accessed: READONLY, APPEND, or UPDATE.

DATABASE SYSTEM system_db access_mode

•

system_db—Tripos-supplied database that becomes a “user” database: FRAGMENT_LIBRARY or GROUP_LIBRARY. (When opened, it becomes the default database.) • access_mode—How database is accessed: READONLY, APPEND, or UPDATE. Using APPEND or UPDATE prevents others from accessing the system database, either directly or through FRAGMENT or ADD GROUP commands, until database is closed. Note: Care should be exercised when modifying the Tripossupplied databases, since much of the program’s operation depends on their contents.

Create a New, Empty Database Menubar: Command Line:

File > Database > New DATABASE CREATE filename

filename—Name for database file. Default extension .mdb is provided automatically. or:

DATABASE XCREATE dbtype filename • dbtype—Database format: MDBMS or MOL2DBMS.

•

filename—Name for database file. Default extension .mdb is provided automatically.

The database that is created becomes the default user database. It is automatically opened in UPDATE mode; there is no need to open the database after creation. If a file already exists with the given file name, you have a choice of replacing the old one or issuing the command again to give another file name. Replacing the old file creates a new file with that same name and deletes the contents of the old file. UIMS2 variable: •

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The DATABASE CREATE and DATABASE XCREATE commands assign a value to the UIMS2 variable DATABASE_NAME.

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11.3.2 Copy Database Contents to a New Database DATABASE TO_MOL2DB source destination source destination

File specification for the source database. File specification for new database, i.e., the Mol2 database. If file exists, you can replace the old one or issue the command again to give another file name. Replacing old file creates a new file with that same name and contents of old file are deleted.

11.3.3 Define a Database Alias DATABASE ALIAS db_name alias db_name alias

Name or alias of an open user database. New alias.

Aliases are useful in conjunction with database qualifiers. An alias can be used in a qualifier instead of the full database name. A database can only have one alias. If the specified database already has an alias, the old alias is overwritten. A user assigned alias is lost when a user database is closed.

11.3.4 Specify the Default Database Menubar: Command Line:

File > Database > Default DATABASE DEFAULT db_name

Database operations are applied to the default database if no database is explicitly specified in a command. UIMS2 Variable: •

DATABASE_NAME.

11.3.5 Close a SYBYL Database Menubar: Command Line: or:

File > Database > Close DATABASE CLOSE DATABASE XCLOSE db_name

If the default database is closed and other databases are open, one is arbitrarily selected as the new default user database.

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Chapter 11. Use Molecule Databases Retrieve Molecules from a SYBYL Database

11.4 Retrieve Molecules from a SYBYL Database 11.4.1 Retrieve a Molecule Menubar: Command Line:

File > Database > Get Molecule DATABASE GET expression [{selection_query}] [mol_area]

•

•

•

expression—Database query expression specifying molecule(s) to retrieve (may include database qualifier, otherwise default database is assumed). selection_query— ASSIGN—Use SELECT and UNSELECT to specify molecules to assign. QUIT—Exit DATABASE GET without loading any molecules. RETRIEVE—Retrieve multiple molecules from open database. To retrieve all molecules in a selection, enter molecule area for first molecule. Other molecules are placed in alphabetical order in consecutive work areas. Previous contents of molecule areas are overwritten. SELECT—Choose subset of currently selected molecules. Selection can be a multi-step process. UNSELECT—Return to set of molecules obtained by last SELECT command. Can be used as many times as SELECT. mol_area—Molecule area where first (or single) retrieved molecule is placed (skipped if no molecule present).

This command behaves differently depending on whether the expression maps to a single molecule, no molecule, or multiple molecules. •

Single molecule, you are prompted for the molecule area to hold the molecule.

•

No molecules, a message indicates that molecule could not be found.

•

Multiple molecules are listed on the terminal and you have access to additional commands to narrow the selection. Retrieved molecules are placed in consecutive molecule areas, starting with the one specified when you entered the command.


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Database Query Expressions on page 170.

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11.4.2 Search for Molecule(s) to Retrieve DATABASE SEARCH search_mode name_expr [action] search_mode

name_expr action

How to search the database: • NAME—Search by molecule name. • MENU—Search using menus. The menus provide a hierarchical structure within databases. The FRAGMENT command, for example, uses a menu structure to control searching of the fragment database. Menus are formed by evaluating molecule groups (sets and classes). A class which is the union of several groups appears on a menu listing the component groups. A group consisting of molecules appears as a menu of molecule names. Selections continue recursively until the final molecule is chosen. Initial query of the molecule/group name (may include database qualifier, otherwise default database is assumed). Varies depending on the search_mode.

This command is useful for browsing through an unfamiliar database, as well as for setting up groups which are otherwise difficult to define.

11.4.3 Database Query Expressions Database query expressions retrieve information about molecules in a database. The molecules can be retrieved, placed into a group, or simply examined by name. Molecules can be identified by whole or partial names, by membership in defined groups, or by a combination of these. The simplest form of a query expression is a molecule name, which specifies a single molecule. When specifying a name to retrieve a molecule from the database, names containing blanks and special characters, such as hyphens or parentheses must be enclosed in double quotes. Names beginning with letters and followed by nothing but letters, digits, or underscores may be used without quotes. This is necessary to distinguish characters in names from operators in database query expressions. The next level of complexity in query expressions allows wildcards in molecule names (but not group names). Finally, operations on groups provide a powerful technique to designate molecules. They can consist of the logical operators union, intersection, difference, and negation and the elements to which they are applied.

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The Venn diagrams below illustrate the logical operators. A, B, and C are general object sets. Shaded areas represent the selected set D which results from the indicated operations. The outer circle represents the total set from which the subsets are chosen. Union

Intersection

Difference

Negation

In either set

In both sets

In first set and not in second

Do not have specified property

D=A+B or D=A,B

D=A&B

D=A-B

D=~A

In database query expressions, operators are evaluated from left to right, with operations of highest precedence evaluated first. The order of operator precedence is (from highest to lowest): Negation Intersection Union, Difference

~ & +–

highest lowest

Parentheses group the elements of the expression for evaluation in a specified order. Examples Retrieve tryptophan from current database and place it in M1. DATABASE GET (tryptophan) m1

Retrieve all molecules whose names begin with t (or T) from current database. For multiple matches, you are asked to select one. DATABASE GET (t*) m1

Retrieve all molecules whose names begin with h (or H) and are members of the group substrate from current database. For multiple matches, you are asked to select one molecules. DATABASE GET (substrate & h*) m1

Retrieve all molecules whose names begin with 1,4,5 T and are members of the group reaction1 or reaction2 (or both). Use parentheses to ensure the union operation takes place before the intersection.

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DATABASE GET (“1,4,5 T*” & (reaction1 + reaction2))

Double quotes around the (partial) molecule name are required since it contains special characters.

11.4.4 View the Database as a Spreadsheet The table of data must pertain to the series of molecules from an open user database. Data can be entered explicitly or calculated from the molecules. Menubar: Command Line:

File > New > Spreadsheet DATABASE TABLE


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The Molecular Spreadsheet Manual for a complete description.

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Chapter 11. Use Molecule Databases Obtain Information on Databases

11.5 Obtain Information on Databases 11.5.1 List All Open Databases DATABASE ALLOPEN Full database names are listed along with aliases given in parentheses. The default user database is denoted.

11.5.2 List Contents of an Open Database Menubar: Command Line:

File > Database > List DATABASE DIRECTORY item_type name_expr • item_type—ANY, CLASS, MOLECULE, SET.

•

name_expr—Expression of names of items to list (may include database qualifier, otherwise default database is assumed).

11.5.3 List Molecule and Group Information for an Open Database DATABASE SHOW item_type name_expr [listing_mode] item_type

ANY, CLASS, MOLECULE, SET.

name_expr

Expression specifying names of items to list (may include database qualifier, otherwise default database is assumed). • BRIEF—Abridged information about selected items, one-item-per-line. • FULL—Detailed listing for each item (for ANY or MOLECULE only).

listing_mode

11.5.4 List Information About an Open Database Default Database: Any Open Database:

DATABASE STATUS DATABASE XSTATUS db_name

Lists contents, including the database filename, alias, format, access mode and the number of molecules, sets, and classes currently defined.

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Chapter 11. Use Molecule Databases Manage Database Content

11.6 Manage Database Content 11.6.1 Add Molecule(s) to a Database Notes: •

The molecule being added must have a name. (See MODIFY MOLECULE NAME to give the molecule a name, or Formats for Specifying Objects on page 202 for syntax of molecule names.)

•

The database must be open in UPDATE mode, or APPEND mode is sufficient if the molecule does not already exist in the database

Menubar: Add to Default Database via Command Line:

File > Database > Put Molecule DATABASE ADD mol_expr [disposition]

•

• Add to Database via Command Line:

DATABASE XADD db_name mol_expr [disposition]

• •

• Name Molecule and Add to Database via Command Line:

mol_expr—Expression defining molecules to add to default user database (either a single molecule area or a comma-separated list of areas). disposition—KEEP or REPLACE original molecule.

db_name—Name or alias of open user database. mol_expr—Expression defining molecules to add (either a single molecule area or a comma-separated list of areas). disposition—KEEP or REPLACE original molecule.

DATABASE SAVE_AS mol_area new_name [disposition]

• •

•

mol_area—Molecule area containing molecule to save. new_name—Name for molecule (may include database qualifier, otherwise default user database is assumed). disposition—KEEP or REPLACE original molecule.


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Open/Save Mol2 Files via the Command Line on page 41.

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11.6.2 Delete Molecule(s) in a Database Menubar: Command Line:

File > Database > Delete Molecule DATABASE DELETE item_type name_expr NO | YES • item_type—CLASS, MOLECULE, SET.

•

name_expr—Expression of names of items to delete (may include database qualifier, otherwise default user database is assumed).

Deletion of groups from a database has no effect on the molecules which were inside those groups. Molecules themselves must be explicitly deleted. The database must be open in UPDATE mode for this command to operate successfully.

11.6.3 Organize Molecules into Groups (Sets and Classes) Additional Information: •

Fragment Library Structure and Contents on page 233

Grouping Mechanisms Molecules in a database can be organized into groups by the user, providing a convenient method for representing relationships between molecules. It is important to recognize the distinction between the sets described below and the sets of atoms, bonds, or substructures. Here the term “set” is used to refer to a collection of molecules, not to a particular molecule’s constituents. Database Sets—A named, static collection of molecules explicitly created by the user. Examples might be groups called “current_project,” “substrates,” or “minimized.” Members of a set may be specified by a database query expression which is evaluated at that time to determine the members of the set. To update the contents of a set, simply give it a new definition which incorporates its own value. For example, the following removes hydroxyproline from the set HYDROPHOBIC. DATABASE DEFINE SET hydrophobic (hydrophobic-hydroxyproline)

Database Classes—Molecules matching a specified database query expression. Once defined, the class is reevaluated each time it is referenced, to reflect the current database contents.

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Define/Modify Definitions of Groups DATABASE DEFINE CLASS | SET name expr comment name expr comment

Name of the class or set. Database query expression (may include database qualifier, otherwise default database is assumed). Short descriptive string explaining significance of class/set.

Note: •

Database must be open in UPDATE mode for this command to operate successfully, or APPEND mode is sufficient if the molecule group does not already exist in the database.

•

Each time a defined class’ name appears in a database query expression, it is reevaluated and its members determined for the database.

•

If a molecule, defined as a member of a set, is deleted, that molecule is automatically removed from the set.


The Database Tutorial on page 159 for an example.

Rename a Group or Molecule Menubar: Command Line:

File > Database > Rename Molecule DATABASE RENAME item old_name new_name • item—CLASS, MOLECULE, SET.

• •

old_name—Current name of group or molecule. new_name—New name for group or molecule.

Notes:

176

•

If new_name for a molecule already exists in the database, you are asked whether or not the new molecule should replace the current one.

•

If new_name for a group already exists in the database, the operation fails.

•

Database must be open in UPDATE mode for this command to operate successfully.

•

Both names may contain a database qualifier. However, the operation fails if the qualifiers do not refer to the same database.

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Reorganize and Compress Database Contents DATABASE REORGANIZE filename filename

Name of the database file (default extension is .mdb).

Reorganizing and compressing the contents of a molecule database allows unused space to be reclaimed. mol2dbms: •

Mol2 files containing more than one molecule are broken into multiple Mol2 files, one molecule per Mol2 file. This “flattens” the database.

•

Mol2 files are renamed so file name matches (or nearly matches) name of molecule in file.

•

Reorganization can decrease access time, but has little effect on database size, since Mol2 databases rarely accrue unused space.

•

Reorganizing a Mol2 database is useful only when the database was created by the user directly from the system shell. This is because Mol2 databases, created and accessed only via the DATABASE command, have neither MultiMol2 files nor misnamed Mol2 files.

•

Whenever SYBYL writes Mol2 files via the DATABASE command(s), they are written with at least 6 digits of precision. If the value of the tailor variable MOL COORD_PLACES is less than 6 (such as the default of 4), it is set to 6 during the operation of the DATABASE command and reset when complete. If, however, the values higher than 6, the tailor’s value is used throughout.

•

Warning: The DATABASE REORGANIZE command creates a new Mol2 database with a temporary name. This name is generated in the directory set by the environment variable TMPDIR. If the variable is not set, the new database is created in the working directory. If this variable is defined in your environment, that is where the new database ends up, and hence appears to be lost.

mdbms: •

A consistency check ensures the database contents match the index structure. This is the only accepted method of recovery for a corrupted database (as indicated by the error message RECORD_KEY_ERROR).

•

Database must not be open by any user when the REORGANIZE command is given. The reorganized database overwrites the old file.

•

Highly active databases should be periodically reorganized to recover unused space. Compressing the files can have a significant impact on access time.

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Chapter 11. Use Molecule Databases Save Database Molecules to Mol2 Files

11.7 Save Database Molecules to Mol2 Files Menubar: Command Line:

File > Database > Write MOL2 File DATABASE WRITE_FILE2 expression selection_query [filename]

•

•

•

expression—Molecule(s) to write out to file(s) (may include database qualifier, otherwise default database is assumed). Multiple molecules are listed in console. selection_query: SELECT expr—Available if multiple molecules are specified. Choose a subset of molecules. Expression provided here is limited to currently specified molecules, even though other database molecules might match. Selection continues until either OUTPUT or QUIT is chosen. UNSELECT—Available if multiple molecules are specified. Return to set of molecules obtained by last SELECT command. UNSELECT can be entered as many times as SELECT was used to narrow the selection. OUTPUT—Write selected set of molecules to file. QUIT—Exit command without writing the file. filename—File to hold molecules (default extension is .mol2). This argument is skipped if QUIT is entered.

Note: Mol2 files written via database operations have at least 6 digits of precision. If the tailor variable MOL COORD_PLACES is set to < 6 (such as the default of 4), it is set to 6 during the operation of the DATABASE command and reset when complete. If the value is > 6, the tailor’s value is used throughout.

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Chapter 11. Use Molecule Databases Database Qualifiers

11.8 Database Qualifiers A database qualifier is added to a query expression to explicitly specify the database to which the expression applies. It consists of a database name (or alias) placed before the query expression, separated from the query by the “!” character. A query expression without a database qualifier automatically applies to the default user database. SYBYL first checks the names of open databases (which can be seen using the ALLOPEN command). If the database qualifier matches a name of an open

database, that database is selected for the operation. If no open database name matches, then the SYBYL checks the alias of any open database. If there is a match, that database is selected for the operation. If no aliases of open databases match, then the qualifier is considered to be invalid. (The same process applies to the open database arguments of the ALIAS, DEFAULT, XADD, XCLOSE, and XSTATUS subcommands.) Note: Double quotes must be used when spaces occur in a database qualifier. Also, if the special character “!” occurs in a molecule name, the molecule name should be enclosed in double quotes. Examples Retrieve tryptophan from the default database and place it in M1. (No database qualifier is needed.) DATABASE GET (tryptophan) m1

Retrieve all molecules whose names begin with t (or T) from the database /usr/ me/mydb.mdb. For multiple matches, select one. DATABASE GET /usr/me/mydb.mdb!(t*) m1

Retrieve the molecule named botulin from the database whose alias is toxins and place it in M3. (A database such as /usr/me/project_xyz/toxins.mdb is automatically assigned the alias toxins when opened.) DATABASE GET toxins!botulin m3

See the OPEN and ALIAS subcommands for additional information about database aliases.

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Chapter 11. Use Molecule Databases The DATABASE Command

11.9 The DATABASE Command The DATABASE command provides functionality to manipulate molecule databases, whether they have been supplied by Tripos or defined by the user. DATABASE functions can be accessed in two ways:

•

Precede each subcommand with the word DATABASE.

•

Type MODE DATABASE to enter the DATABASE mode. To exit this mode, type either the end-loop character (|) or ENDMODE. Selecting another menu category also exits the DATABASE mode. When in DATABASE mode, other SYBYL commands can be accessed by preceding them with COMMAND.

Below is a list of the DATABASE subcommands: ADD ALIAS ALLOPEN CLOSE COMMAND CREATE DEFAULT DEFINE DELETE DIRECTORY

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ENDMODE GET MATCH_ALIGN (QSAR Manual) OPEN RENAME REORGANIZE SAVE_AS SEARCH SHOW STATUS

SYSTEM TABLE TO_MOL2DB WRITE_FILE WRITE_FILE2 XADD XCLOSE XCREATE XSTATUS

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Chapter 11. Use Molecule Databases System Utilities

11.10 System Utilities Since system commands like rm and cp behave differently when operating on regular files versus directories (without additional flags), the following system shell scripts are provided in $TA_BIN. •

db_rm removes molecular databases of either format: db_rm db1 ... dbN

•

db_cp copies a molecular database of either format: db_cp source_db target_db

The format of target_db is the same as that of source_db. target_db is overwritten if it already exists.

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Chapter 12.

Manage SYBYL Sessions •

Save a SYBYL Session on page 184 •

What is Saved in a Session?

•

What is Not Saved in a Session?

•

Details About Saved Backgrounds

•

Open (Restore) a Saved Session on page 189

•

Delete a Saved Session on page 189

•

Open a New Session on page 189

•

Close a SYBYL Session on page 190

•

Record and Play Back SYBYL Operations on page 191

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•

Record SYBYL Operations in a File

•

Play Back a File of Recorded Operations

•

Insert a Pause in a Recorded File

•

Read Command Input From a Text File

•

Record the Output from a Single Command

•

Record the Console Dialogue of a Session

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Chapter 12. Manage SYBYL Sessions Save a SYBYL Session

12.1 Save a SYBYL Session A SYBYL session, in its current state, can be saved in a specified directory. This allows you to return to SYBYL at a later date and continue your work from the point where you saved the session. See Open (Restore) a Saved Session on page 189. Save the Session Menubar:

File > Save Session (Ctrl+S) Or File > Save Session As

Icon: Command Line:

or

on the Standard toolbar.

SESSION SAVE dir_name

Each SYBYL session is saved in a directory. The default name for a session directory is the current date and time (dd_mmm_yyyy_hh_mm). The extension .ses is appended automatically. Saving a session changes the default directory to that of the saved session. The first Save Session ( )operation prompts for a directory name. Subsequent Save Session operations for the same session, whether newly created or restored from a previously saved session, overwrite the same directory. Use Save Session As (

) to save the current session to a new directory.

Save the Session and Exit SYBYL Command Line:

SESSION SQUIT dir_name

Additional Information: To specify a single default location (other than “current working directory”), use the environment variable SAVE_SESSION_DIR, which must be set prior to starting SYBYL.

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12.1.1 What is Saved in a Session? A SYBYL session is a directory of files that contain the full specification necessary to restore the session at a later time. For that purpose the following are saved. •

All molecules in their displayed state are saved to individual .mol2 files that include for all atoms their show/hidden status, color, labels, and rendering mode.

•

Data necessary to preserve rotatable bond angles and to restore dynamic hydrogen bonds, distance and bump monitoring.

•

Surfaces and ribbons associated with molecules as well as their show/ hidden status and color.

•

Toolbars: position of all toolbars, visible status of all icons, user-defined icons.

•

Screen settings: •

Global and individual rotations and translations as well as scale

•

Screen mode: full, quartered, etc.

•

View mode: mono, orthographic, relaxed, and crossed stereo, (but not stereo in a window) and associated settings

•

Depth cue and Z-clipping

•

Font, color and lighting

•

Tailor variables and parameter files (.tpd)

•

Tables based on: •

Molecule databases (including analyses).

•

UNITY hitlists

•

MDL SD/RD files

•

Dynamics history files

•

Conformational search angle files

•

Imported data

Also saved with tables are analyses and supporting files for CoMFA, EVA, and CoMSIA columns. If the row labels are 2D structures when saved, then restoring also shows these labels. •

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The following types of background objects: •

Rulers

•

MOLCAD surfaces

•

Protein rendering

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•

Biopolymer ribbon

•

Hbond

•

Multiple volume surfaces

•

Potential

•

Dots

•

QSAR contours

12.1.2 What is Not Saved in a Session? •

Table graphs

•

Tables based on:

•

•

•

UNITY database

•

Biopolymer loop search

•

ProTable

Backgrounds not supported: •

Generalized Surfaces

•

Isosurfaces

•

Contour display created surfaces-CoMFA region

•

MOPAC

•

AMPAC

•

Force Field constraints

Annotations

12.1.3 Details About Saved Backgrounds MOLCAD Surfaces •

The surface style (lines, dots, etc.) and the current coloring property are retained.

•

If the color of a MOLCAD surface is changed with the BACKGROUND COLOR command, the color will not be restored correctly.

Protein Rendering •

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The following settings are taken from the time of creation: •

The opaque/transparency (TAILOR!RENDER!SURFACE_TYPE)

•

Display of alpha helices (TAILOR!RENDER!HELIX_DISPLAY)

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•

Determination of secondary structure elements (TAILOR!RENDER!SEC_STR_SRC)

•

All other settings of TAILOR!RENDER are taken from the tailor.save file at the time of the session saving:

•

If the coloring is by table column, it will not be retained.

Biopolymer Ribbon •

The number of strands and color are retained.

•

Setting for TAILOR!RIBBON!RIBBON_WIDTH is taken from the tailor.save file at the time of the session saving.

Hydrogen Bonds •

The atom set and color are retained.

•

All settings of TAILOR!HBONDS are taken from the tailor.save file at the time of the session saving.

•

The .dsp file is not saved, as the background will be recreated upon restoration of the session.

QSAR Contours •

The graph field file must be saved during the contour creation. This file is saved if the contour was created from the QSAR GRAPH FIELD command. If the View CoMFA dialog was used, the Save to File(s) check box must be on.

•

The surface type used at creation is retained using the TAILOR!CONTOUR!DISPLAY_AS setting.

•

All TAILOR!TABLE and TAILOR!GRAPHS values are taken from the tailor.save file at the time of the session saving.

•

The .dsp and .cnt files are not saved, as the background will be recreated upon restoration of the session.

Volume/Mvolume •

The volume color and surface type used at creation are retained using the TAILOR!CONTOUR!DISPLAY_AS setting.

•

Settings of TAILOR!VOLUME are taken from the tailor.save file at the time of the session saving. However, volumes created with TAILOR!VOLUME!MAP_RANGE set to FIXED_RANGE are not restorable.

•


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•

The filename originally used to create the .dsp/.cnt file is not retained. A default name is used to guarantee that more than one of these surface types can be restored without needing to prompt the user.

Potential •

The surface type used at creation is retained using the TAILOR!CONTOUR!DISPLAY_AS setting.

•

Settings of TAILOR!POTENTIAL are taken from the tailor.save file at the time of the session saving.

•


•

The filename originally used to create the .dsp/.cnt file is not retained. A default name is used to guarantee that more than one of these surface types can be restored without needing to prompt the user.

•

These backgrounds are not restorable with TERM NO.

•

The coloring method used at creation is retained.

•

Settings of TAILOR!DOTS are taken from the tailor.save file at the time of the session saving.

•

The .dot file is not saved, as the background will be recreated upon restoration of the session.

•

The filename originally used to create the .dot file is not retained. A default name is used to guarantee that more than one of these surface types can be restored without needing to prompt the user.

Dots

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Chapter 12. Manage SYBYL Sessions Open (Restore) a Saved Session

12.2 Open (Restore) a Saved Session Previously saved SYBYL sessions can be restored using either of the following. Menubar:

Icon:

File > Open Session (Ctrl+O) The 5 most recent sessions are listed on the File menu in reverse chronological order. on the Standard toolbar.

Command Line:

SESSION RESTORE dir_name

Each saved SYBYL session is stored in a directory with the .ses extension. See Save a SYBYL Session on page 184. During restoration: •

The current working directory is changed to the location of the restored session’s directory.

•

Prompts are also presented regarding the deletion of any currently displayed molecules, backgrounds, and tables before continuing.

12.3 Delete a Saved Session To delete a saved session simply delete the session directory.

12.4 Open a New Session Open a new SYBYL window where you can perform work independently of the current session. Menubar: Icon:

File > New > Session (Ctrl+N) on the Standard toolbar.

If licensing does not allow for an additional SYBYL window a dialog will inform you that the session limit has been reached. See License Requirements for SYBYL Basics on page 8.

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Chapter 12. Manage SYBYL Sessions Close a SYBYL Session

12.5 Close a SYBYL Session If you have multiple SYBYL sessions open simultaneously you must close each of them individually. File > Close Session When closing a SYBYL session you will be prompted whether to save it s Closing a session performs the following operations: •

Prompts whether to save the current session so that the current state of SYBYL reloaded at a later time. See Manage SYBYL Sessions on page 183 for more details.

•

Deletes all molecules and background objects (Edit > Delete Everything).

•

Closes all spreadsheets and associated databases.

•

Reset the directory that the default when SYBYL was launched.

Closing a session does not exit SYBYL.

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Chapter 12. Manage SYBYL Sessions Record and Play Back SYBYL Operations

12.6 Record and Play Back SYBYL Operations SYBYL includes scripts for tracking commands and playing back recorded operations. These are useful for documenting a session and when tracking potential problems in the use of SYBYL. It is important to activate these options at the beginning of your SYBYL session. A collect/take file consists of a series of command lines where each command must appear on a single logical line. Lines are terminated by an end-loop character (|) unless the last character on the line is a back slash (\). The following characters, when first on one line, have special meaning in a collect file: #

ignore the line, typically used for comments,

% if current session is interactive ask user for confirmation before continuing, typically used to pause during playback. Additional Information: •

Automatic Command Execution at SYBYL Startup on page 238

12.6.1 Record SYBYL Operations in a File When this option is enabled, all commands and arguments are captured into a file which can be replayed to reproduce a session. The file closes automatically at the end of the SYBYL session. Menubar: Command Line:

Options > Record Macro COLLECT action [filename]

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action: APPEND—Reopen existing file and continue journaling. COMMAND—Force collection of next command even if

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collection was suspended. FILTER—ON/OFF; whether to collect all SPL constructs. FORCE_RESUME—Resume journaling even if multiple SUSPEND commands were made. ON—Enable journaling of command input in file. OFF—Stop journaling of commands and close file. RESUME—Cancel last SUSPEND. SUSPEND—Temporarily suspend journaling without closing file. filename—File to receive journaled commands. Default extension is .col.

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To store actions of menu picks in a collect file, first issue the command MENU COLLECT ON.

Only one COLLECT file can be open at a given time. UIMS2 Variable: •

UIMS2_COLLECT_FILE—Name of the current collect file.


Record the Console Dialogue of a Session on page 194

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Read Command Input From a Text File on page 193

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Insert a Pause in a Recorded File on page 193

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Play Back a File of Recorded Operations on page 192

12.6.2 Play Back a File of Recorded Operations A recorded session can be used to repeat a series of commands on several different molecules, to replay a demonstration script, or to recover one’s position lost as a result of system failure. Menubar: Command Line:

Options > Load Macro TAKE filename

When an incomplete command line is encountered in the file, interactive prompting takes place to finish the command before proceeding to the next command line. Additional Information:

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Record SYBYL Operations in a File on page 191

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Read Command Input From a Text File on page 193

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Insert a Pause in a Recorded File on page 193

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12.6.3 Insert a Pause in a Recorded File PAUSE delta_time delta_time

Number of seconds to pause program execution.

By inserting this command into the recorded session file, you can halt program execution for a specified number of seconds or indefinitely, if delta_time is set to zero. In this way, you can give the user ample time to read the comments. PAUSE is used in preparation of demonstration scripts. Note: These scripts cannot be played back in menu mode. As an alternative to PAUSE, inserting the WAIT command suspends execution until either C (continue), G (go), or Q (quit) is entered. Enter either command at the keyboard during the recording session or edit the file afterwards. Additional Information: •

Record SYBYL Operations in a File on page 191 to prepare a script.

•

Play Back a File of Recorded Operations on page 192 to play back a prepared script.

12.6.4 Read Command Input From a Text File TTY filename Input is read from the specified file (file extension must be included) until an end-of-file condition is encountered. The text in the file is executed as if it was manually entered by the keyboard. This is convenient when generating command procedures without the use of the COLLECT command. (The tutorial files (.demo) have this format.) Warning: TTY does not understand command context as does the TAKE command. Thus any mistakes in the TTY file are faithfully executed. Additional Information: •


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12.6.5 Record the Output from a Single Command The text output from a single command can be sent to a file. This is useful for storing lengthy output of commands such as minimizers, LIST, TOPOGRAPHY, etc. CAPTURE filename command filename

File to receive output generated by specified command. No default file extension. A single SYBYL command with all its arguments.

command Additional Information: •

List Coordinates, Distances, or Angles on page 149.

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List Information About SYBYL Objects on page 155

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12.6.6 Record the Console Dialogue of a Session When this option is enabled, the complete dialogue is recorded in a file. Program prompts, user responses, commands, and program output are recorded in this file. It can be used to document sessions with the program as an adjunct to a laboratory notebook. The file closes automatically at the end of the SYBYL session. Menubar: Command Line:

Options > Log Session PHOTO status [filename]

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status: ON—Record console dialogue to specified file. Infor-

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mation is first stored in a buffer. By default, buffer is automatically flushed to the file as soon as it is full. OFF—Terminate recording. FLUSH—Write all currently buffered PHOTO information immediately to file. Future I/O flushing is not affected by this command. LINEBUFFER—Line buffer pending and all future PHOTO I/O, data is flushed continuously to file. LINEBUFFER is off initially. If you turn PHOTO OFF then back ON, you must explicitly turn on LINEBUFFER again. filename—File to receive the console dialogue. There is no default extension.

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UIMS2 Variable: •

UIMS2_PHOTO_FILE—Name of the current photo file.


Record the Output from a Single Command on page 194

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Chapter 13.

SYBYL Objects and Their Expressions •

Definitions of SYBYL Objects on page 198

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Formats for Specifying Objects on page 202

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Naming Rules and Special Characters in Expressions on page 202

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Substructure Specification on page 206

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Set Specification on page 207

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Molecule Specification on page 207

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Molecule Area Specification on page 207

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Conformational Specifications on page 210

Create Complex Expressions on page 211

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Chapter 13. SYBYL Objects and Their Expressions Definitions of SYBYL Objects

13.1 Definitions of SYBYL Objects Molecule Areas Work spaces which hold structures being manipulated. Areas are designated by the letter M followed by an integer. Any number of molecule areas can be defined at any time, since SYBYL can handle an unlimited number of molecules simultaneously. They may be assigned in arbitrary order, and will hold any named entity supplied either from an external file, through construction internally, or from a database. A molecule area may contain a single atom, multiple fragments, water molecules, ions, or other components, and structures with unfilled valences. Atoms The fundamental building blocks of molecules. You may name them arbitrarily and specify their type. Parameters for over 50 different atom types are provided in SYBYL. An extended list of more than 103 atom types is available in the file $TA_DEMO/metals.tpd. You can easily expand this number by adding new types of your own. Atoms can exist as bonded entities or singly. Bonds Connection between atoms to form molecules. Bond types (single, double, triple, amide, aromatic, dummy, or non-chemical) are determined by the types of atoms they join. Bond types determined automatically by the program can be overridden to accommodate exceptional circumstances in a particular molecule. Substructures Group of atoms in which it is possible to reach any atom from any other atom along a bonded pathway. No atom in a molecule can belong to more than one substructure. A substructure may be a single atom, molecule fragments, functional groups, or monomers in a polymer. They are included in the molecular description to help subdivide problems into manageable sizes and easily reference pieces of the molecule. Substructures are created and managed by SYBYL without intervention. For example, when constructing a biopolymer from monomers defined in a dictionary or reading one in from a standard biopolymer structural file such as the Protein Data Bank, each residue is a substructure. An example of the substructure assignment for a short peptide sequence is shown below (substructure boundaries marked by parentheses).

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In the case of non-polymers, the only control you have over the creation and designation of substructures is in the order you construct the molecules or in fragments chosen from the standard fragment library. All fragments in the fragment library are designated as substructures. There is no unique assignment of substructures to molecules. One person might assign them differently from another. For example, the figure below shows two copies of a single molecule which have been partitioned differently into substructures. Neither one is necessarily a better choice than the other; they are merely different.

Features Features are molecular characteristics. They can be based on atoms, other features, or contain other information. •

Center of mass, centroid, extension point, line, normal, plane, and various UNITY features

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Force field angle, distance, range, periodic boundary conditions and torsional constraints

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Sets, including aggregates

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Search anchor atom, rotatable bonds, ring closure and distance constraints

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Crysin unit cell parameters and space group

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Associated data file locations

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Associated dictionaries

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Alternate atom types

Rings SYBYL detects the formation and records the presence of rings at all times in all molecules. Rings have wide-ranging implications for conformational manipulations as well as modification of internal parameters, such as bond lengths and angles, and they play an important role in identifying similarities among molecules. •

Internal ring—A ring completely contained within a substructure. Atoms and bonds in an internal ring are distinguished by the character * next to their name in the atom or bond list.

•

External ring—A ring which spans substructure boundaries. Typically occur in polymers which are cross-linked (e.g., a peptide structure which has one or more disulfide bridges). Atoms and bonds in an external ring are distinguished by the character @.

The figure below illustrates both internal and external rings. The boxes delineate substructure (monomer) boundaries in this peptide fragment. The phenyl group in the phenylalanine monomer is an internal ring since it occurs completely within the confines of a substructure. The heavy, dark bonds indicate a ring formed by the cross-linking of the peptide by a disulfide bridge between two cysteine monomers. It is termed an external ring because it crosses substructure boundaries.

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Sets Named collections of objects substructures, atoms or bonds used for identifying and naming important groups in a molecule. A set can be used as a shorthand notation for groups of atoms, bonds, or substructures which are referenced often. •

Static sets—Membership is identified at the time of definition. Once specified, this membership does not change unless one of the elements (atoms, bonds, substructures) is deleted from the molecule. For example, identify the amino acids in the active site of an enzyme and name them for quick access.

•

Dynamic sets—Membership is defined in terms of a rule and evaluated at the time of reference. For example, the environment around a particular atom in a molecule can be defined as a set using a sphere of specified radius. As the molecule’s conformation is manipulated, the membership in the set may change. When you reference this set’s name, the contents of the volume are identified by evaluating the rule at that time. The built-in sets in SYBYL are dynamic sets: Aromatic, H-bonds, Backbone, Sidechain, Rings, Bumps, and Metals.

See Sets in SYBYL on page 215 for more details.

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Chapter 13. SYBYL Objects and Their Expressions Formats for Specifying Objects

13.2 Formats for Specifying Objects 13.2.1 Naming Rules and Special Characters in Expressions There are a number of general naming conventions and special symbols used to denote the various objects in SYBYL. Molecules

Atoms, Substructures, Sets, Features

Chains

* @

Names can be arbitrarily long and complex, containing any characters (alphanumeric, underscore,...). Enclose name in double quotes (“ ”) if it starts with a numeric character, has special characters, or a space. No limit on the number of characters in a name. Tripos recommends 7 characters for atoms and substructures, and 31 for sets and features. Names must start with an alphabetic character, but are case insensitive (characters are held internally in uppercase). Names may contain digits, underscores (_), and apostrophes (') in any position after the first. • CA CA12—Valid atom names • 1C C(1)—Invalid atom names Note: Only set names are required to be unique. Names are restricted to 4 characters and must start with an alphanumeric character. If the name begins with an alphabetic character, the following characters can be A-Z, 0-9, _, $ or '. If the name begins with a numeric character, the following characters must also be numeric. They may contain underscores in any position after the first position and before the last position. Match any number of characters of any type. Match a single character of any type.

In addition to the conventions listed above, there are object-specific protocols. These are discussed in the following sections:

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Substructure Specification on page 206

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Set Specification on page 207

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Molecule Specification on page 207

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Molecule Area Specification on page 207

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Conformational Specifications on page 210

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Add Molecule(s) to a Database on page 174 for adding molecules to a database.

13.2.2 How to Specify an Atom Expression Many SYBYL commands operate on a specified group of atoms represented as atom_expr in the command descriptions. To supply an atom or group of atoms in a written expression, use any or a combination of the following methods. Specify by:

Notes and Examples:

Atom ID Atom Name

Atom ID numbers. HIS1.CA—CA atom in residue HIS1. HIS1.*—All atoms in substructure HIS1.*. *.CA—All atoms named CA in all substructures. *—All atoms in default molecule area. A*.C1—All atoms named C1 in substructures whose name begins with A. —All sp2 nitrogens. —All oxygens (equivalent to O). —All carbons, plus any atom type beginning with a C (e.g., calcium, chlorine, etc.). Notes: • Types are case insensitive. The modifier identifies different forms of the same element (not necessarily hybridization states). • See the Force Field Manual for a list of predefined SYBYL atom types. M1—All atoms in molecule area 1. M2(atom_expr)—The atoms in M2 identified by the atom expression.

Atom Type

Molecule Area

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Substructure and Set

Connected Path

Substructure Path

Chain

{PHENYL}—All atoms in substructure(s) named PHENYL. {5}—All atoms in substructure with group ID 5. {HELIX}—All atoms in set named HELIX. {HYDROPHOBIC}—All atoms in set named HYDROPHOBIC. {HIS*}—All atoms in all histidine residues (same as {HIS*}). {SPHERE(PHE20.CA, 10.5)}—All atoms in 10.5 Å sphere

around the α-carbon of residue PHE-20. Notes: • Substructures are searched first for name matches, then, if none match, all forms of both local and global sets are searched. Only sets with atoms as objects are valid. • For biopolymers, a number in braces indicates the sequence number, which may differ from the substructure ID. C1:C10—All atoms on all paths from C1 to C10, inclusive. 5:8—All atoms on all paths from atom 5 to atom 8, inclusive. Notes: • If rings are in the path, all paths through the rings are searched. • Connected paths where the endpoint atoms are members of rings are ambiguous and may not produce the desired selections. {PHE10:HIS25}—All atoms in all monomers of a biopolymer chain from PHE10 to HIS25, inclusive. {1:10}—All atoms in all monomers of a chain from residue 1 to 10, inclusive. Notes: • Braces ({}) identify all atoms in the substructures on the path, not just atoms in the bonded pathway. • Only monomers on the direct backbone path between the first and second monomer are identified, even in the presence of rings. • Sets are not defined in terms of connectivity, only the substructure name list is searched for matches to determine the origin and targets of the scan. A/HIS1.CA—CA atom in residue HIS1 of chain A. Note: Only one chain specification per expression. Chain specification cannot be combined with single or range ID numbers because IDs constitute unique identifiers.


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Naming Rules and Special Characters in Expressions on page 202.

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13.2.3 How to Specify a Bond Expression Several SYBYL commands operate on a specified group of bonds represented as bond_expr in the command descriptions. To supply a bond or group of bonds in a written expression, use any or a combination of the following methods. Bond ID Atom Name

Bonds Type

Molecule Area Substructure and Set

Substructure Path

Chain

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Bond ID numbers. CA—All bonds connected to the CA atom(s). O*—All bonds to atoms whose name starts with an O. Note: Name one or both endpoint atoms. —All double bonds. —All aromatic bonds. Note: SYBYL bond types are: single , double , triple , aromatic , and amide . M1—All bonds in molecule area 1. M2(bond_expr)—The bonds in M2 identified by the bond expression. {MONTYPE(TYR)}—All bonds in substructure(s)/monomer(s) of type tyrosine. {5}—All bonds in substructure with group ID 5. Note: Substructures are searched first for name matches, then, if none match, all forms of both local and global sets, are searched. Only sets with bonds as objects are valid. {PHE10:HIS25}—All bonds in all monomers of a biopolymer chain from PHE10 to HIS25, inclusive. {1:10}—All bonds in all monomers of a chain from residue number 1 to residue 10, inclusive. Notes: • Braces ({}) identify all atoms in the substructures on the path, not just atoms in the bonded pathway. • Only monomers on the direct backbone path between the first and second monomer are identified, even in the presence of rings. • Sets are not defined in terms of connectivity, only the substructure name list is searched for matches to determine the origin and targets of the scan. A/HIS1.CA—Bonds involving CA atom in residue HIS1 of chain A. Note: Only one chain specification per expression. Chain specification cannot be combined with single or range ID numbers because IDs constitute unique identifiers.

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Specific Bond

C1=C10—Bond between atoms C1 and C10. HIS1.CA=HIS1.CB—Bond between alpha (CA) and beta (CB)

carbons in residue HIS1. In this case, endpoint atoms must be unique. This technique can only be used to designate one unique bond. 3=7—Bond between atoms whose IDs are 3 and 7. Note: Atoms must be bonded directly to one another. Additional Information: •


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13.2.4 Substructure Specification Substructure specification can be accomplished using several mechanisms discussed in the following table. Note: Enclosing a substructure’s name or ID in braces ({}) is only required when specifying the name of a set to select the substructures of interest. This forces both the substructure name list and set name list to be searched for matches with the input name. Otherwise, only the substructure name list is searched. ID Number

Substructure Name

Substructure Path

Chain

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For biopolymers, ID refers to monomer sequence (e.g. 15 in ALA15). For small molecules, ID refers to substructure ID. A hash or pound sign (#) preceding a number is interpreted as a substructure ID, even for biopolymers. {RING*} or RING*—All substructures whose name starts with RING. Note: The name must start with an alphabetic character. Digits, underscores, or apostrophes may follow. {PHE10:HIS25}

•

In biopolymer, all monomers along direct backbone path from PHE10 to HIS25. • In small molecule or sequence numbers, all substructures on all paths from PHE10 to HIS25. A/ALA15—Substructure with name of ALA15 in chain A. Note: Only one chain specification per expression. Chain specification cannot be combined with single or range ID numbers because IDs constitute unique identifiers.

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Set Name

{MONTYPE(ALA)}—All substructures that are monomers of type alanine. MONTYPE is a built-in set. Note: Only sets with substructures as objects are valid and appear on the menu.



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13.2.5 Set Specification Braces ({}) are not necessary for set designation, but are accepted for consistency (e.g., RING_A {HELIX_*})

13.2.6 Molecule Specification A molecule’s full name, or a fraction thereof, and the wild character (*) can be used. Enclose names that start with a numeric character, contain special characters, or a space, in double quotes. ”alpha_chymotryp“ ”active isome #3“ ”5HT“

13.2.7 Molecule Area Specification The default molecule area is the one in which you are normally performing all operations. To perform operations on another molecule without changing the default area (e.g., to measure intermolecular distances), specify the molecule area before the expression, which is enclosed in parentheses: M2(C3)

This example specifies all atoms named C3 in molecule area M2. The molecule area name (M#) associated with a molecule remains the same during a session.

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13.2.8 Monomer Sequence Specification Monomer sequence specifications can be divided into two categories, generic and specific (refer to the Sequence Expression dialog for making your selection with the mouse). Generic Monomer Sequences A generic monomer sequence is a list of monomer names connected by an equal sign (=). Monomer names may be given as the normal monomer name (1 to 4 characters long), or as the one character code, as defined in the macromol dictionary. gly=ala=phe e=p=f

The sequence may contain numerical repeat counts to indicate repetition of a sequence (the sequence to be repeated must be enclosed in parentheses). 2(arg)=val=phe=3(ser=cys)

is equivalent to: arg=arg=val=phe=ser=cys=ser=cys=ser=cys

and also equivalent to: arg=arg=val=3(ser=cys)

Specific Monomer Sequences A specific monomer sequence is a sequence in the default molecule area. The following forms are allowed: mon=mon=mon= mon:mon:mon:

* molecule area(sequence)

Connected linear sequence of monomers. * in place of a monomer matches any monomer. Guided range of monomers. All monomers on a direct path along the backbone of the biopolymer between adjacent monomers are selected. The entire biopolymer. Sequence in stated molecule area.

“mon” may be:

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General monomer name matching any monomer of that type (e.g. phe)

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Specific monomer name detected by the presence of digits and matching only a monomer with that exact name (e.g. phe27)

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Sequence number matching any monomer with that sequence number as part of its name (e.g. 18)

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The < or > character matching the beginning and ending monomers of a chain, respectively.

Note that monomer names, as defined in the dictionary, may not contain digits, and each monomer in a molecule should contain a sequence number in its name (usually indicating its position in the chain). Sequence specifications can be combined by separating them with commas. To specify a sequence on a particular chain of the biopolymer, prefix the specification with the chain name followed by a slash (e.g. A/*). To specify a sequence in a molecule area other than the default area, enclose the entire specification in parentheses, and prefix it with the molecule area (e.g. M3(glu3)). As an example, consider the nucleic acid fragment: a1=c2=g3=g4=u5=a6=c7=a8=g9

Entering this:

Selects this:

g3:a6 a=c 6:8 * c=*=g u,a1=c2 7:>

g3=g4=u5=a6 a1=c2, a6=c7 a6=c7=a8 a1=c2=g3=g4=u5=a6=c7=a8=g9 c2=g3=g4, c7=a8=g9 u5, a1=c2 c7=a8=g9

A number refers to the monomer with that sequence number as part of its name (e.g. 8 in GLY8). As a special case, to identify the monomer by its substructure ID number, precede the ID number with a hash or pound sign (#). This is particularly useful when dealing with unresolved ends of protein chains. Additional Information: •

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13.2.9 Conformational Specifications This type of data specification dictates the conformation of all or part of a biopolymer. Conformational state names, or conformational angle names with the angle value (in degrees) are both acceptable. Conformational states and angles are defined in the dictionary. (Note: Only the minimum number of initial characters of the name required to distinguish it from other conformational states or angle names needs to be typed.) Separate multiple specifications with commas. The formats for conformational specifications are as follows: •

statename—Assigns angle values as defined in the given state.

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angle1=xxx,angle2=yyy—Alters the present angles to the specified values.

Examples: alpha_helix alph phi=-58.0,psi=-47.0 staggered,beta=120

The valid state names are given in the following table. alpha_helix

none

three/10_helix

aturn

pi_helix

trans

beta_sheet

random

trans6

b_like

random_12

turnI

c5

random_13

turnII

c7ax

random_14

turnIII

c7eq

random_16

turnVIa

cis

ribbon_2_7

turnVIb

invaturn

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Chapter 13. SYBYL Objects and Their Expressions Create Complex Expressions

13.3 Create Complex Expressions Objects (atoms, bonds, etc.) can be combined, using standard operations, to yield complex expressions. When SYBYL operation prompts you for an object (atom, bond, etc.), you can use any of the methods described in the previous section, which yields exactly one object when interpreted. When you are prompted for an object expression, you may enter a group of objects. Object expressions allow you to combine various objects to produce a resultant set, which is the exact portion of the molecule that you want to manipulate. Additional Information: •


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Formats for Specifying Objects on page 202

13.3.1 Logical Operators Expressions can consist of the logical operators union, intersection, difference, and negation (represented by the symbols + or comma, &, - and ~, respectively) and the elements to which they are applied. In the discussions which follow, an abstract definition of a logical operation is given using A, B, and C as general object sets and D as the general resultant set. The general form of the allowable expression is very similar to the algebraic form of mathematical equations. Parentheses group the elements of the expression for evaluation in a specified order. The Venn diagrams below illustrate the logical operators. Shaded areas represent the selected set D which results from the indicated operations. The outer circle represents the total set from which the subsets are chosen. Union

Intersection

Difference

Negation

In either set

In both sets

D=A+B or D=A,B

D=A&B

In first set and not in second D=A-B

Do not have specified property D=~A

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Note: Since SYBYL uses spaces as delimitors between commands and arguments, spaces are not allowed in expressions. Examples Union Locate all carbons and oxygens in a molecule and color them green. COLOR ATOM + GREEN

Color all alpha carbons, other carbons, nitrogens, and oxygens red (these atoms make up a peptide backbone). COLOR ATOM CA,C,N,O RED

Intersection Identify atoms in the active site of an enzyme and also in a helical secondary structure: LIST ATOMS {HELIX*}&{ACTIVE_SITE} BRIEF

This presumes that the sets {HELIX} and {ACTIVE_SITE} have been defined previously. Locate all carbons which have a partial charge between 0.0 and 0.10 in a particular molecule and color them red. COLOR ATOM &{CHARGE(0.0,0.1)} RED

This example makes use of one of the built-in sets: {CHARGE}. Difference Color all atoms not in the backbone of a biopolymer yellow: COLOR ATOM *-{BACKBONE} YELLOW

The asterisk selects all atoms and then the backbone atoms are subtracted. {BACKBONE} is a built-in set defined for all polymers. List all carbons not sp3 hybridized: LIST ATOMS - BRIEF

Negation Select sidechain atoms for a biopolymer, exclude backbone atoms: COLOR ATOM ~{BACKBONE} YELLOW

This is functionally identical to the color command shown as the difference operator example.

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13.3.2 Parentheses and Grouping of Operations When grouping operations into more complex expressions, keep in mind that intersection has a higher precedence than union, just as multiplication has precedence over addition in algebra. Parentheses are used to force evaluation of the expression in a particular order by grouping objects and operators.

Examples Display only heteroatoms in a molecule, combine a union operation with a negation operation: DISPLAY ~(,)

Locate all carbons and oxygens which are in hydrophobic residues of a protein: DISPLAY (+)&{HYDROPHOBIC}

The set {HYDROPHOBIC} must have been defined previously.

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Chapter 14.

Sets in SYBYL A Set is a named collection objects: atoms, bonds, or substructures. Examples in the context of a biopolymer are sidechain atoms, backbone bonds, co-crystallized water molecules, active site. A set can be used as a shorthand notation for groups of atoms, bonds, or substructures which are referenced often. Some sets are closely associated with the particular molecules for which they are defined (local sets), while others may be applied in a blanket fashion to any molecule (global sets). Once applied to a particular molecule, the definitions of all sets are stored in the molecular description along with the coordinates and all other molecular data. When you reference a set name in the context of an operation, the members of the defined set are automatically identified as the object of the action. If the request is for atoms or bonds, the specified substructures are expanded to their respective atom or bond constituents automatically. The diagram below shows sets used in SYBYL and their interrelationships.

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Global Sets on page 217—Set whose definition is applicable on a system-wide basis, i.e., it may be applied to any molecule. of special interest are the Global Sets in the Biopolymer Dictionary on page 218.

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Local Sets on page 220—Created for specification of objects in a particular molecule. Membership is associated only with that molecule.

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Dynamic Sets on page 222—Uses a rule to define membership. Membership is determined when it is referenced, by interpreting the expression in the context of the current molecular description. Both local and global sets can exhibit dynamic properties.

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Built-in Sets on page 223—Always a dynamic global set and based on properties or geometrical relationships which are subject to change. Can be applied to atoms, bonds, or substructures.

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Chapter 14. Sets in SYBYL

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Static Sets on page 228—Membership is identified at the time of set definition.

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Aggregates—Local sets, always static, and user-defined. If defined by a dynamic rule, it is immediately evaluated and membership becomes static. Aggregates are recognized by the minimizer as groups of atoms and bonds whose relative geometry is not to be optimized. (See the discussion of Aggregates in the Force Field Manual for additional information.)

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User-Defined Sets—Either dynamic (local or global) or static sets created by the user. Global sets defined by the user are always dynamic and are used exactly as those carried in the macromol dictionary. In some cases, a set can be defined equally well as static or dynamic, depending upon whether membership is likely to change during the course of the project. For example: •

Alpha_helical region of a peptide.

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Chair and boat conformations of six-membered rings in a polycyclic structure.

•

Charge range for atoms carrying an electrostatic charge between the values of 0.1 and 0.5 esu.


216

•

Working with Sets on page 229

•

How to Use the Atom Expression Dialog on page 75 for examples of how to use defined sets

•

Definitions of SYBYL Objects on page 198

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Chapter 14. Sets in SYBYL Global Sets

14.1 Global Sets Global sets are dynamic sets not directly associated with any specific molecule. They may be defined at any time and can be applied to any molecule. They are always of the dynamic type. By their very nature they cannot include specific objects. Once applied to a particular molecule, they are copied to that molecule’s set list and remain associated with it, unless explicitly deleted. For example, the definition of POSITIVELY_CHARGED. Global sets which are built into the program are typically defined in the macromol dictionary. When the dictionary is opened, sets are available for use automatically. Additional Information: •


14.1.1 Define a Global Set DEFINE GLOBAL_SET object_type object_expr name comment object_type object_expr name

comment

Class of object to be members of set: ATOM, BOND or SUBSTRUCTURE. Set of objects of indicated class (evaluated only when set is referenced). Name for set. Must be unique. First character must be alphabetic and a maximum of 30 additional characters must be alphanumeric or underscores (_). Arbitrary string associated with set.

14.1.2 Modify a Global Set Menubar: Create/Modify Comment via Command Line:

SYBYL-X 1.1

Not accessible from the menubar. MODIFY GLOBAL_SET COMMENT set_expr {comment}

• •

set_expr—Expression indicating set to modify. comment—Descriptive string, may contain any characters and be of arbitrary length. Use double quotes when entering spaces or special characters.

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Change Definition via Command Line:

MODIFY GLOBAL_SET DEFINITION set_expr {object_exp}

• •

set_expr—Expression indicating set to modify. object_expr—Rule for determining membership of the dynamic set. Global sets must be dynamic, hence the definition must be in terms of a general expression rather than specific members. The class of objects selected by a global set cannot be altered by this procedure, only the definition.

Note: If a global definition is modified, it is modified in all instances associated with the molecules in memory. If the local (molecule-associated) copy is modified, it is no longer considered related to the global definition from which it was derived. In that case, modification of the global set of the same name does not affect the local copy.

14.1.3 Delete a Global Set REMOVE GLOBAL_SET set_expr set_expr

Expression indicating set to remove, may include the wildcard character (*). For example, to remove both g1 and g2, enter g* or the expression g1,g2.

Note: If a global definition is deleted, its copies associated with the molecules in the work areas are also deleted. If the local (molecule-associated) copy is modified, it is no longer considered related to the global definition from which it was derived. In that case, deletion of the global set of the same name does not affect the local copy.

14.1.4 Global Sets in the Biopolymer Dictionary Although you can define a new global set as it becomes necessary, several global sets are already associated with the macromol dictionary and automatically become available for use when the dictionary is opened. The table below provides a complete listing of global sets currently available in the macromol dictionary, accompanied by objects to which they apply and a defining expression explaining how the various sets were created.

218

Name

Objects

Defining Expression

ACIDIC

Substs

{MONTYPE(asp,glu,tyr)}

BASIC

Substs

{MONTYPE(his,arg,lys)}

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Name

Objects

Defining Expression

BLOCK

Substs

{MONTYPE(ace,nme,pyr,amd,for,nmt,nmm,cme,mes ,ees,boc)}

BULKY

Substs

{MONPROP(MOL_WT,140,9999)}

CALPHA

Atoms

CA

CAP

Substs

{MONTYPE(amn,cxl,ami,cxc)} for proteins {MONTYPE(hb,he)} for DNA and RNA

DISULFIDE

Bonds

sg-cb-hg-lpg1-lpg2,sd-cg-hd-1pd1-1pd2

DNA

Substs

{MONTYPE(dA,dG,dC,dT)}

HYDROPHOBIC

Substs

{MONTYPE(gly,ala,ile,leu,met,phe,pro, trp,val)}

MOD_AA

Substs

{MONTYPE(abu,aib,arz,asz,bal,cym,cyx,glz, hcx,hcy,hid,hie,hip, hpr,hse,hyp,lyz,nle,nva, orn,orz,phg,pse,psm,psz,ptm,pty,ptz)}

NEUTRAL

Substs

{MONTYPE(tyr,his,asn,cys,gln,ser,thr)} + {HYDROPHOBIC}

POLAR

Substs

{MONTYPE(asp,glu,tyr,asn,gln,thr,ser,cys, his,lys,arg)}

PURINE

Substs

{MONTYPE(dG,dA,rG,rA)}

PYRIMIDINE

Substs

{MONTYPE(dC,dT)} for DNA {MONTYPE(rC,rU)} for RNA

RNA

Substs

{MONTYPE(rA,rG,rC,rU)}

STD_AA

Substs

{MONTYP(ala,arg,asp,asn,cys,glu,gln,gly,his, ile,leu,lys,met,phe,pro,ser,thr,trp,tyr,val)}

SUGAR

Substs

{MONTYPE(glb,mab,maa,gaa,gab,frb,fra,dra, drb,rba,rbb)}

Note: Atomic weights correlate with the latest accepted figures from IUPAC and NIST. The average difference is 0.01% of the old values. In the cases of unstable atoms, the values for the most stable isotope are used. •

IUPAC: Pure Appl. Chem. 2003, 75, 1107-1122

•

National Institutes of Standards and Technology (NIST)


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Dictionary Files description in the Biopolymer Manual.

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Chapter 14. Sets in SYBYL Local Sets

14.2 Local Sets A local set consists of objects in a particular molecule. Membership is associated only with that molecule. Local sets may be defined by any user at any time. Examples are the definition of a protein’s active site and aggregates used during minimization. Local sets may be dynamic or static. •

Dynamic Sets on page 222

•

Static Sets on page 228

When an atom or a bond involved in a local set is removed from the molecule, the set membership is automatically updated. Additional Information: •


14.2.1 Modify a Local Set Menubar: Create/Modify Comment via Command Line:

Change Definition via Command Line:

Change Name via Command Line:

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Edit > Sets > Modify Set MODIFY LOCAL_SET COMMENT set_expr {comment}

• •

set_expr—Expression indicating set to modify. comment—Descriptive string, may contain any characters and be of arbitrary length. Use double quotes when entering spaces or special characters.

MODIFY LOCAL_SET DEFINITION set_expr {object_expr [merge]}

• •

set_expr—Expression indicating set to modify. object_expr—Membership (for a static set) or rule for determining membership (for a dynamic set). • merge—NO/YES, for static sets only, whether to add to or replace current definition. For dynamic sets, there is no merge option; they are completely redefined by this command. MODIFY LOCAL_SET NAME set_expr {name}

• set_expr—Expression indicating set to modify. • name—Name for set. First character of set name must be alphabetic and may be followed by up to 30 additional characters, including alphabetic, numeric, and the underscore (_). Names must be unique among all other (GLOBAL or LOCAL) sets and also among substructures.

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Chapter 14. Sets in SYBYL Local Sets

14.2.2 Delete a Local Set Delete a user-defined local set, static or dynamic, from a molecule’s description. Menubar: Command Line:

SYBYL-X 1.1

Edit > Sets > Delete Set REMOVE LOCAL_SET set_expr

•

set_expr—Expression indicating the set(s) to remove, may include wildcard character (*). For example, to remove both s1 and s2, enter s* or the expression s1,s2.

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Chapter 14. Sets in SYBYL Dynamic Sets

14.3 Dynamic Sets A dynamic set is a group of objects whose membership is evaluated dynamically (only when the set name is used in a command or is referenced by an application routine). A standard object expression is analyzed at the time of reference to determine the current set of objects meeting the requirements of the expression. The expression must be valid for the type of object the set is to contain. Because objects are not permanently assigned to a set of this type, dynamic sets are most often used to monitor properties of molecules which are subject to change, such as conformation, charge, strain energy among many others.

14.3.1 Define a Dynamic Set Menubar: Command Line:

Edit > Sets > Create Dynamic Set DEFINE DYNAMIC_SET object_type object_expr name comment

• • •

•

object_type—Class of object to be members of the set: ATOM, BOND or SUBSTRUCTURE. object_expr—Expression of objects, of indicated class, to include in set (evaluated only when set is referenced). name—Unique name for set. First character must be alphabetic with a maximum of 30 more characters (alphanumeric or underscores (_)). comment—Comment string.

14.3.2 Examples of Dynamic Sets Define all substructures (monomers) within 10 Å of atom C1 in residue A17 as members of the set called ACTIVE_SITE: DEFINE DYNAMIC_SET SUBSTRUCTURE {SPHERE(A17.C1,10)} \ active_site “10Å radius around A17”

If the atoms are manipulated (e.g., conformations are modified), membership in this set can change. Color the atoms that are members of the dynamic set ACTIVE_SITE: COLOR ATOM {active-site} MAGENTA

The membership is evaluated at the time of reference according to the definition rule. Substructures belonging to the set are expanded into their constituent atoms for the execution of the command.

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Chapter 14. Sets in SYBYL Built-in Sets

14.4 Built-in Sets The membership of a built-in set is determined at the time it is referenced. Built-in sets may not be created, removed, or altered by the user. Built-in sets differ from the general dynamic set types: •

Evaluation rules are built into the program.

•

They may require one or more arguments to direct their evaluation. Required arguments are specified in parentheses after the set name, separated with commas. For example, {SPHERE(C2,5)} specifies all atoms within 5 Å of atom C2.

The table below contains a complete listing of built-in sets currently available in SYBYL, the forms in which they are invoked (commands and arguments required, if any), explanations, and examples. AROMATIC

{AROMATIC(atom_expr)}

•

Atoms in the same aromatic system as the specified atom(s).

Atoms

LIST ATOM {AROMATIC(9)} BRIEF BACKBONE

{BACKBONE}

•

Atoms belonging to the backbone as defined in the macromol dictionary.

Atom Set

COLOR ATOM {BACKBONE} RED

•

Bonds

{BACKBONE}

Bonds belonging to the backbone as defined in the macromol dictionary. SCAN {BACKBONE} BIOPOLYMER

{BIOPOLYMER(option1,option2,…)}

•

Substructures in a biopolymer. Options are: • PROTEIN—Selects amino acids in protein chains (including modified amino acids). It is similar to

Substructure

• • • • •

{SEQUENCE(*)} DNA—Selects nucleic acids in DNA chains. RNA—Selects nucleic acids in RNA chains. COFACTOR—Selects cofactor substructures, as

defined in the biopolymer dictionaries. WATER—Selects water substructures, as defined in the biopolymer dictionaries. LIGAND—Selects substructures not included in the above categories and not a carbohydrate, as defined in the biopolymer dictionaries.

COLOR SUBSTRUCTURE {BIOPOLYMER(LIGAND)} CYAN

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BUMPS

{BUMPS(atom1,atom2)}

•

Atoms in one group having van der Waals contacts with atoms of the other group. van der Waals parameters stored in the file $TA_ASCTABLES/ATOM_DEF are used. Use TAILOR SET GENERAL BUMPS_CONTACT_DISTANCE to define the cutoff distance. Negative values allow overlap of van der Waals spheres, positive values prohibit it. Default is 0.0 Å.

Atoms

COLOR ATOM {BUMPS(atom1,atom2)} MAGENTA CHARGE

{CHARGE(minimum,maximum)}

•

Atoms having a residual charge in the specified range.

Atoms

COLOR ATOM {CHARGE(-.05,-.01)} BLUE CHIRAL

{CHIRAL(atom_expr,RS)}

•

Atoms of the specified chirality or pro-chirality. Specify the atoms to search as an expression. Chirality is indicated by the second argument as: R, S, RS, PRO_R, PRO_S, or PRO_RS. If RS or PRO_RS is entered, all centers are included in the set. The default is to search all atoms (*) for all chiral centers (RS).

Atoms

COLOR ATOM {CHIRAL(CA,S)} YELLOW FINDCONF

{FINDCONF(state1+state2+,sequence)}

•

Monomers having the specified conformational state(s) as defined in the macromol dictionary. Entering a sequence limits the search to the specified regions of the biopolymer (“*” searches whole biopolymer). Separate conformational states by plus signs.

Substructures

LABEL SUBSTRUCTURE {FINDCONF(ALPHA_HELIX,*)} H_CONN_VIS_HEV

{H_CONN_VIS_HEV(atom_expr,type)}

Hydrogen atoms that are connected to visible heavy atoms. Valid types include: ALL, HBOND, NONHBOND, POLAR, or NONPOLAR. It is used to display hydrogens the Protein Viewer and in the Molecule Display Options tool. HBOND

{HBOND(atom_expr,type)}

•

Atoms of the specified type participating in hydrogen bonds. Valid types include: ALL, DONOR, ACCEPTOR, or HYDROGEN. Definitions for the donor and acceptor atoms are in the parameter table $TA_ASCTABLES/ ATOM_DEF as H_ACCEPTOR and H_DONOR fields.

Atoms

LIST ATOM {HBOND(1+2+3+4+5+6,donor)} BRIEF

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METAL

{METAL}

•

Atoms with a metallic ordinal number (according to the periodic table). This set also includes metal atoms in cofactors.

Atoms

COLOR ATOM {METAL} PURPLE MONPROP

{MONPROP(keyword,minimum,maximum)}

•

Monomers having the specified property as identified by a keyword and (optional) minimum and maximum values. Enter only the keyword to select all monomers having that keyword. Enter the keyword and a minimum to select monomers with the keyword whose value matches the minimum. The keyword may be any arbitrary string. Values may be real, integer, or string. Properties are stored in the macromol dictionary (molecular weight is stored as MOL_WT).

Substructures

LABEL SUBSTRUCTURE {MONPROP(MOL_WT,150,200)} MONTYPE

{MONTYPE(type1,type2,...)}

•

Monomers of the specified type(s). Types are defined in the macromol dictionary. As many types as desired may be specified as arguments. An asterisk (*) specifies all substructures that are monomers.

Substructures

LABEL SUBSTRUCTURE {MONTYPE(A,T)} POSSIBLE_HBOND

{POSSIBLE_HBOND(atom_expr,type)}

•

Atoms of the specified type which can potentially participate in hydrogen bonds. Valid types include: • ALL • DONOR—Potential H bond donor atom, attached to a hydrogen or has at least one free valence. • ACCEPTOR—Potential H bond acceptor. • HYDROGEN—Hydrogen attached to an H bond donor.

Atoms

LIST ATOM {POSSIBLE_HBOND(*,all)} BRIEF RINGS

{RINGS(atom_expr,type)}

•

Specified atoms which are included in rings of the specified type. Types include: • I—Internal rings (completely contained within a substructure). • E—External rings (crossing substructure boundaries). • EI (IE)—Either internal or external. If no arguments are entered, defaults to {rings(*,EI)}.

Atoms

COLOR ATOM {RINGS(*,E)} BLUE

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•

Bonds

{RINGS(bond_expr,type)}

Specified bonds which are included in rings of the specified type. Types include: • I—Internal rings (completely contained within a substructure) • E—External rings (crossing substructure boundaries) • EI (IE)—Either internal or external. If no arguments are entered, defaults to {rings(*,EI)}. COLOR BOND {RINGS(*,I)} RED

•

Substructures

{RINGS(substructure_expr,type)}

Substructures in the expression, which are included in rings of the specified type. COLOR SUBSTRUCTURE {RINGS(*,E)} YELLOW SEQUENCE

{SEQUENCE(sequence1,sequence2,)}

•

Atoms in monomers of the specified sequence(s). Monomers are defined in the macromol dictionary. See Specific Monomer Sequences on page 208 for more information.

Atoms

COLOR ATOM {SEQUENCE(GLY=PRO,GLY=GLY)} BLUE COLOR ATOM {SEQUENCE(A/1:25)} RED COLOR ATOM {SEQUENCE()} MAGENTA

•

Bonds


Bonds in monomers of the specified sequence(s). Monomers are defined in the macromol dictionary. SCAN {SEQUENCE(GLY=PRO)}

•

Substructures


Monomers in the specified sequence(s). Monomers are defined in the macromol dictionary. LABEL SUBSTRUCTURE {SEQUENCE(A=T=C,T=*=U)} SIDECHAIN

{SIDECHAIN}

•

Atoms belonging to sidechains as defined in the macromol dictionary.

Atoms

COLOR ATOM {SIDECHAIN} RED

•

Bonds

{SIDECHAIN}

Bonds belonging to sidechains as defined in the macromol dictionary. SCAN {SIDECHAIN}

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SPHERE

{SPHERE(atom_expr,radius)}

•

Atoms falling within sphere(s) of the specified radius. The expression defines the sphere center(s). When multiple atoms are selected, the final set is the union of sets of atoms within spheres of indicated radius about each center. All spheres have the same radius.

Atoms

COLOR ATOM {SPHERE(ALA23.CA,10)} MAGENTA

•

Bonds


Bonds falling within sphere(s) of the specified radius. The expression defines the sphere center(s). When multiple atoms are selected, the final set is the union of sets of bonds within spheres of indicated radius about each center. Note: Only bonds with both endpoint atoms in the sphere are accepted. All spheres have the same radius. SCAN {SPHERE(N15,8)}

•

Substructures


Substructures falling within sphere(s) of the specified radius. The expression defines the sphere center(s). When multiple atoms are selected, the final set is the union of sets of substructures within spheres of indicated radius about each center. Note: Substructure is accepted, even if only one of its atoms falls within the sphere. All spheres have the same radius. LABEL SUBSTRUCTURE {SPHERE(G16,12)} SUBST_SPHERE

{SUBST_SPHERE(atom_expr,radius)}

Atoms, bonds, or substructures falling within sphere(s) of the specified radius. The expression defines the sphere center(s). When multiple atoms are selected, the final SUBST_SPHERE set is the union of sets of substructures included in spheres of indicated radius about each center. Note: Substructure is accepted, even if only one of its atoms falls within the sphere (identical to sphere for substructures). TO_ATOMS

{TO_ATOMS(atom_expr)}

•

Bonds with one or both atoms in the specified expression.

Bonds

SCAN {TO_ATOMS(CA)} CYAN


SYBYL Atom Types in the Force Field Manual.

•

Global Sets in the Biopolymer Dictionary on page 218

•


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Chapter 14. Sets in SYBYL Static Sets

14.5 Static Sets Membership of a static set is determined by a standard object expression analyzed at the time of definition. Once specified, this membership does not change unless one of the elements is deleted from the molecule. In this case, it is automatically removed from the set as well and the membership is redefined. With the exception of set members deleted from the molecule, every time you reference a static set, the same elements are selected. Only local sets can have static properties. The latitude with which you can define members of a static set provides great flexibility in the manipulation of molecular data. For example, static sets can define: •

Active site portion of an enzyme (select atoms or monomers involved)

•

Diene and dienophile portions of a molecule designed to undergo an intramolecular cyclo-addition reaction

•

Glycone and aglycone portions of a nucleoside

•

Acyclic precursor region of what becomes part of a larger structure upon cyclization

In addition, in SYBYL’s Biopolymer program, static sets are automatically generated when molecules are read in from Protein Data Bank files.

14.5.1 Define a Static Set Menubar: Command Line:

Edit > Sets > Create Static Set DEFINE STATIC_SET object_type object_expr name comment

• •

•

•

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SYBYL Basics

object_type—Class of object to be members of set: ATOM, BOND or SUBSTRUCTURE. object_expr—Expression of objects, of indicated class, to include in set. object_expr is not retained with set definition. name—Unique name for set. First character must be alphabetic with a maximum of 30 additional characters (alphanumeric or underscores (_)). Default is the current name plus and underscore and number. comment—Comment string. If you modify the set, the default comment is the current comment plus _new.

SYBYL-X 1.1

Chapter 14. Sets in SYBYL Working with Sets

14.6 Working with Sets When you modify, list, or remove sets, SYBYL displays a dialog containing the defined sets. Click the molecule in the list and use the selection tools to specify the desired sets to modify, list, or remove. Highlighting a set in the list also highlights the atoms in that set in the SYBYL window. The examples below show the dialogs invoked for a protein. Options > List > Sets

Select a molecule:

SYBYL-X 1.1

Options > List > Global Sets

Select the molecule area and molecule from the list. Buttons to assist in the selection of sets: select all, invert selection, clear selection.

SYBYL Basics

229


Chapter 15.

Libraries of Chemical Groups and Fragments SYBYL provides functional groups and fragments that allow you to easily build most molecules. In some instances, however, you may need to have additional fragments included in the standard library. These operations can be accomplished once you know a little about the SYBYL file structure. In this section, you will find: •

Group Library Structure and Contents on page 232

•

Fragment Library Structure and Contents on page 233

•

Using the Fragment Library: Load Fragments on page 109

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Chapter 15. Libraries of Chemical Groups and Fragments Group Library Structure and Contents

15.1 Group Library Structure and Contents As supplied by Tripos, the group library contains a variety of small functional groups frequently used in the construction of molecules. Each functional group is represented as a distinct molecule within a SYBYL database: ALLYL CN CO2MINUS EPOXY N-AMIDE N-PROPYL NH2 OCO OO SH SO2N VINYL

AMIDE CO CS ETHYL N-BUTYL N3 NO OH PHENYL SO SO2O

BENZYL CO2 CYCLOHEXYL ISOPROPYL N-N N=N NO2 ONO SEC-BUTYL SO2 T-BUTYL

For convenience, the molecules in the library are given these same names. Each group has a unique attachment point, internally equal to the root atom of the root substructure of the molecule. Externally, a convention has been established which identifies the attachment point as the first atom in the molecule name (except for Phenyl). The internal convention must be observed for all user-added groups in order for commands like ADD GROUP to function properly. Additional Information:

232

•


•

Chemical Group on page 128 for how to add functional groups to structures

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Chapter 15. Libraries of Chemical Groups and Fragments Fragment Library Structure and Contents

15.2 Fragment Library Structure and Contents As supplied by Tripos, the fragment library contains approximately 200 small molecules (fragments) which can be used to build organic molecules with good initial geometries. Each fragment is the result of averaged crystallographic observations (i.e., averaged geometries from the Cambridge data file). The library is organized in a hierarchical fashion, using both “sets” and “classes”. If you are unfamiliar with this terminology, read about database grouping mechanisms in Organize Molecules into Groups (Sets and Classes) on page 175. The basic idea is that each molecule in the fragment library is a member of one (or more) static database sets. These sets form the lowest level of the hierarchy, and group together those molecules which are very closely related in structure and/or function. At higher levels of the hierarchy, those molecules related in a more general sense appear in the same group. This produces a structure which looks like an inverted tree, with general categories at the top diverging into more and more specific categories until, at the bottom, a single molecule is left. For example, one of the high-level categories is “Cyclic Systems”—clearly a very general grouping. From this category you may descend to heterocyclic systems with two rings, then to those with one heteroatom, then to 56 ring systems. At this point you reach the lowest level categories, those consisting of static sets of actual molecules where, in this case, you would find indole or benzofuran. Access: •

File > Get Fragment

•

FRAGMENT

•

See Load Fragments on page 109.

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The lowest level groups—those which contain the actual molecules—are static sets, while all higher level categories are dynamic classes, defined as the union of those groups directly under them. Thus the “56 Systems” are contained in a static set, such as FIVESIX, but the group which corresponds to “1 Heteroatom” in the above diagram is a dynamic class defined as the union of FIVESIX and SIXSIX (FIVESIX+SIXSIX). Similarly, “Heterocyclic 2 Rings” is a dynamic class defined as the union of “1 Heteroatom”, “2 Heteroatoms” and “>2 Heteroatoms”. Tripos’ standard fragment library contains about 200 molecules partitioned into 44 static sets, and categorized into a hierarchy comprised of 17 dynamic classes. Below is the full listing of sets and classes provided by Tripos to organize the fragment library. In the listing, the dynamic classes are represented in italic script, all others are static sets.

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A: Acyclic Functions • • • • • • • •

AA: Carbon Only AB: Function N AC: Function O AD: Function S AE: Function NO AF: Function SO AG: Function PO AH: Other

B: Cyclic Functions •

•

• •

•

SYBYL-X 1.1

BA: Homocyclic, 1 Ring BAA: Saturated BAB: Unsaturated, 1 Double Bond BAC: Unsaturated, 2 Double Bonds BAD: Unsaturated, >2 Double Bonds BAE: Aromatic BB: Homocyclic, 2 Rings BBA: Saturated BBB: Unsaturated BC: Homocyclic, 3 Rings BD: Homocyclic, 4 Rings BDA: Steroids BDB: Other BE: Heterocyclic, 1 Ring BEA: 1 Heteroatom • BEAA: 5 Membered Ring, Saturated • BEAB: 5 Membered Ring, Unsaturated • BEAC: 6 Membered Ring, Saturated • BEAD: 6 Membered Ring, Unsaturated • BEAE: Other BEB: 2 Heteroatoms • BEBA: 5 Membered Ring, Saturated • BEBB: 5 Membered Ring, Unsaturated • BEBC: 6 Membered Ring, Saturated • BEBD: 6 Membered Ring, Unsaturated BEC: >2 Heteroatoms

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•

•

BF: Heterocyclic, 2 Rings BFA: 1 Heteroatom • BFAA: 56 Systems • BFAB: 66 Systems BFB: 2 Heteroatoms • BFBA: 56 Systems • BFBB: 66 Systems BFC: >2 Heteroatoms BG: Heterocyclic, 3 Rings BGA: 1 Heteroatom • BGAA: 656 Systems • BGAB: 666 Systems • BGAC: 676 Systems BGB: 2 Heteroatoms • BGBA: 666 Systems • BGBB: 676 Systems BGC: >2 Heteroatoms

C: Amino Acids D: Nucleic Acids • DA: Bases • DB: Ribose Monophosphate E: Biologically Important Molecules • EA: Vitamins • EB: Sugars • EC: Lipids

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Chapter 16.

Advanced SYBYL Features As you gain familiarity with SYBYL you may want to explore the following features: •

Automatic Command Execution at SYBYL Startup on page 238

•

Execute a SYBYL Command on Multiple Molecules on page 239

•

Define Markush Atoms on page 241

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Chapter 16. Advanced SYBYL Features Automatic Command Execution at SYBYL Startup

16.1 Automatic Command Execution at SYBYL Startup You may customize the SYBYL interface for your own use by storing in a file the SYBYL instructions to be executed every time you start a new session. This file, called sybyl.ini, must be placed in your home directory ($HOME on Linux or Documents and Settings on Windows). This file can typically be used to load your preferred font type and size or to specify the colors used when working with UNITY features. For additional information turn to the Toolkit Manual:

238

•

Customizing SYBYL

•

A Sample sybyl.ini File

SYBYL Basics

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Chapter 16. Advanced SYBYL Features Execute a SYBYL Command on Multiple Molecules

16.2 Execute a SYBYL Command on Multiple Molecules Use Default Molecule Area:

ALLMOLS sybyl_command

Use Non-Default Molecule Area:

ALLMOLS BASE mol_area

Use Subset of Molecules:

ALLMOLS GROUP mol_area_expr This command must precede the ALLMOLS command

The command syntax must include a molecule area (as a regular argument or as part of an atom or bond expression). The default is M1. The ALLMOLS command applies the SYBYL command, substituting the default area as needed, to every molecule area in turn. If you do not know the entire command syntax, you are prompted for information needed to complete the command. This command must precede the ALLMOLS command line. It designates the molecule area to substitute in the loop. You then must include that molecule area in the ALLMOLS command.

line. It designates the set of molecules to which subsequent ALLMOLS commands will apply. Note: The operation will affect all molecules in the GROUP as well as the BASE molecule, even if it is not specifically included in the GROUP. BASE and GROUP remain in effect until they are changed or until the end of the

session. The operation you want to perform must be possible on all molecules, otherwise an error message is issued for every failed attempt. For example, coloring all alpha helices will fail on molecules that do not contain that secondary structure. Examples: The following examples assume four molecules in M1, M2, M3, M4, respectively, all having backbone, heteroatoms, and hydrogen atoms. Label all heteroatoms in all molecules on the screen. BASE and GROUP are assumed to have their default values of M1 and *, respectively. ALLMOLS LABEL HETERO M1(*)

Color backbones in the molecules in M1, M3, and M4 yellow. BASE is assumed to have its default value of M1. (The molecule in M2 is unchanged.) ALLMOLS GROUP M1,M3,M4 ALLMOLS COLOR ATOM M1({BACKBONE}) YELLOW

SYBYL-X 1.1

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239

Chapter 16. Advanced SYBYL Features Execute a SYBYL Command on Multiple Molecules

Remove hydrogens from the molecules in M2, M3, and M4. (The molecule in M1 is unchanged.) ALLMOLS BASE M2 ALLMOLS GROUP M3,M4 ALLMOLS UNDISPLAY M2()

240

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SYBYL-X 1.1

Chapter 16. Advanced SYBYL Features Define Markush Atoms

16.3 Define Markush Atoms Markushes are lists of groups of atoms which can provide constrained variability in a pattern or structure. For example, a markush atom that represents all halogens would be: Hal:F|CL|BR|I

When a SYBYL session is started predefined Markushes are loaded from $TA_ROOT/tables/markush.defs. However, using the methods discussed below, you can create your own set of Markush definitions, save them to a file, and load them instead. •

Define a Markush on page 241

•

Delete a Markush on page 242

•

List Currently Defined Markushes on page 242

•

Load Markush Definitions from a File on page 242

•

Modify a Markush Definition on page 242

•

Save a Markush Definitions to a File on page 242

16.3.1 Define a Markush Note: A newly defined Markush is only available during the current SYBYL session, unless it is saved to a file and then loaded. Menubar:

Applications > Library Design > Markush > Define

Command Line:

MARKUSH DEFINE name definition

• •

SYBYL-X 1.1

name—Name for new Markush atom. definition—SLN defining the Markush (refer to the SLN Manual). To create an opaque Markush (a Markush with an empty definition), simply press the carriage return at the prompt for the definition.

SYBYL Basics

241

Chapter 16. Advanced SYBYL Features Define Markush Atoms

16.3.2 Delete a Markush Menubar:

Applications > Library Design > Markush > Delete

Command Line:

MARKUSH DELETE name

16.3.3 List Currently Defined Markushes List the contents of the file of Markushes that is currently loaded (by default this is $TA_ROOT/tables/markush.defs). Any Markushes that have been defined during the current SYBYL session are included in the list as well. Menubar:

Applications > Library Design > Markush > List

Command Line:

MARKUSH LIST

16.3.4 Load Markush Definitions from a File Menubar:

Applications > Library Design > Markush > Load

Command Line:

MARKUSH LOAD filename

16.3.5 Modify a Markush Definition Any modifications to Markush definitions will not exist beyond the current SYBYL session unless they are saved to a file. Menubar:

Applications > Library Design > Markush > Modify

Command Line:

MARKUSH MODIFY name definition

• •

name—Name of Markush to modify. definition—New SLN defining the Markush.

16.3.6 Save a Markush Definitions to a File For any user-defined Markushes to be available during subsequent SYBYL sessions, they must be saved to a file and then loaded during that session.

242

Menubar:

Applications > Library Design > Markush > Save

Command Line:

MARKUSH SAVE filename

SYBYL Basics

SYBYL-X 1.1

SYBYL Basics Index A Abort a command Access help

Attributes remove from atom 121 from bond 127 from stereo atom from stereo bond

31

21

Acidic global se

218

132 132

Automatic command execution

Add atom 118 bond 125 chain 119 features and constraints 145 group 128 hydrogens 120 pseudo-atoms 119 rawatom 118 Aggregate sets 216 ALLMOLS 239 Alternate atom types Amide bond

123

205

Amino acid global sets

219

Angle between planes 150 measure 148 modify 127 Aromatic bond

205

Aromatic built-in set 223 Atom add 118 chirality attribute 130 expression rules 203 modify 122 naming conventions 203 rawatom 118 remove 121 renumbering 144 selecting 61 SYBYL object definition 198 Atom expression dialog 67 Atom types alternate set 123 modify 123

Average molecule

Backbone built-in set

223 Basic global set 218 Basics introduction

7

Bibliography chirality assignment 130 SHAKE algorithm 136 BIOPOLYMER sets 218 Biopolymer built-in set Block global set

223

219

Bond add 125 angle list 149 attributes 130 definition of types 71 expression rules 205 length list 149 naming conventions 205 remove 126 remove attributes 127 selecting 61 stereo attributes 130 SYBYL object definition 198 type modify 127 Bond expression dialog 67 Building small molecule Built-in sets

Attach chain 119,

Bumps

SYBYL-X 1.1

136

B

Atomic coordinate topography 149

128

238

111

223 Bulky global set 219

SYBYL Basics Index-243

built-in set

224

Customize start up

C C-alpha carbon global set 219

Chain of atoms 119 Change molecule name 133, 176 substructure name 129 Charge built-in set 224 modify 122

130

Chiral built-in set

224

Chirality atom attribute check 101 invert 131

130

Class define in a database

175

Clear the screen 89 Collect commands into a file Command mode special characters

191

31

Conformation naming conventions 210 SCAN 136 valid state names 210 Connectivity quick bonds Console

125

30

Continuous Drawing Mode Cancel point of attachment 112 Conventions (see Names) Coordinates list 149 MODIFY

D DATABASE

219 CAPTURE 194 Center of mass 138 Centroid 139 Cap global set

CHIRAL

238

180

Database add molecules 174 classes 175 close 168 copy contents to new database 168 copy database directories 181 create empty database 167 create table 172 DATABASE command list 180 define alias 168 define class or set 176 example 160 delete 175 deleting database directories 181 get a molecule 169 grouping mechanisms 175 list contents of open database 173 molecule and group information open databases 173 open 167 rename 176 reorganize contents 177 save as 174 save to Mol2 file 178 search 170 example 163 sets 175 show status 173 specify default database 168 tutorial 159 unlocking 166

173

dbtranslate dialog 44 options dialog 46 dbtranslate O/S utility see UNITY manual use in MDL Mol conversion

43

dbunlock O/S utility 166 Default molecule area

122

Copy 55 molecule area contents 55 Creating small molecules

111

Index-244 SYBYL Basics

54

Defining center of mass 139 centroid 139 dynamic set 222 extension point 140 global set 217

SYBYL-X 1.1

line 141 normal 142 plane 143 static set 228 UNITY features 145

E Edit text files 49 EDITOR 49

Delete atom attributes 121 atoms 121 bond attributes 127 connected atoms 121 hydrogens 121

Environment variable EDITOR 49 SAVE_SESSION_DIR 184 TA_HIDE_UNLICENSED_PRODS

Deleting all atom attributes 121 all bond attributes 127 atom 121 bond 126 center of mass 139 centroid 139 extension point 140 global set 218 line 141 local set 221 molecule in a database 175 non query atoms 145 normal 142 plane 143 stereo atom attributes 132 stereo bond attributes 132 substructure 129 SYBYL session 189 UNITY feature 146 Difference operator in a database 171 in object expressions Directory list database contents

211

173

Display area 52 diagram 53

219 DNA global set 219 Double bond 205 Dummy atom 138, 139, 142, 143 Dynamic set 222 Disulfide global set

(see also Local sets) SYBYL object definition

SYBYL-X 1.1

Evaluating center of mass 139 centroid 139 extension point 140 line 141 normal 142 plane 143 Extension point

140

External ring SYBYL object definition Extract structures from molecule area

201

200

55

F Features center of mass 138 centroid 139 extension point 140 line 141 normal 142 plane 143 SYBYL object definition UNITY 145

199

File formats .demo file 193 convert between molecular formats 44 File selection dialog

Distance measure 148 modify 127

26

34

Files convert between molecular formats 44 edit 49 reading/writing MDL Mol file 42 SD file 42 SLN 42 Files created CAPTURE 194 COLLECT 191 DATABASE 167 WRITE_FILE2 MDL Mol files 42

178


Mol2 39 SD files 42

with SYBYL

Internal ring SYBYL object definition

Fill valences 120 Findconf built-in set FRAGMENT

224

Intersection operator in a database 171 in object expressions

109

Fragment library 233 structure and contents

200

211

Invert chirality 131

233

Freeze coordinates before merging

J 56

Join

Fuse ring 134 tutorial 103

groups or molecules 135 Journal COLLECT command 191 PHOTO command 194

G Geometry measure 147 modify 127 Global dictionary set set 217

13

K Kollman atom types

218

L

Grid SKETCH

Libraries

117 Group library 232 add 128 SKETCH 115 structure and contents

123

231

License requirements SYBYL basics 8 Line List

232

object information

155

Load molecule 16, 33 commands 41 fragment library 16

H H_CONN_VIS_HEV built-in set

141

224

Hardcopy 156

Local set 220

Hbond built-in set

224 Height measurement 148 Help 21 special characters 31 Hide menu options 26

Logical operators in object expressions difference 211 grouping 213 intersection 211 negation 211 union 211

Hydrogens add 120 delete 121

Lone pair MODIFY

Hydrophobic global set

M

219

Manage SYBYL session 183

I Information report on atom, bond, or substructure

122

130 MARK_ZE isomerism 130 Markush 241 MARK_RS isomerism

154

Interacting


SYBYL-X 1.1

MDL Mol convert to molecular spreadsheet convert to UNITY hitlist 43 MDL Mol file read/write files

42 MDLMOL command 42 Measure angle 148 distance 148 height 148 plane angle 150 torsion 148 UNITY features 151 Menubar 26 shortcuts

Molecule expression dialog 74

Merge 56 atoms 56 exceptions 56 merging features 56 non-unique atom 56, 58 non-unique atoms example set 57 structures 56 unique atom 56

Monomer sequence expression rules 208 sequence naming conventions 208 Monprop built-in set 225 Montype built-in set 225

58

225

Modified amino acid global set 219 Modify angle 127 atom 122 bond 127 distance 127 global set 217 local set 220 molecule 133 substructure 129 torsion 127 UNITY feature 146

43

Molecule build 95 defining features 138 deleting in a database 175 evaluating features 138 expression rules 207 extracting atoms 55 modify 95, 133 naming conventions 207 reading files 33, 34

SYBYL-X 1.1

N Name atom 203 modify 122 bond 205 chain 209 conformation specification general conventions 202 local set 220 molecule area 207 molecules 207 monomer sequence 208 generic 208 specific 208 set 207 substructure 206 Negation operator in a database 171 in object expressions

Mol2 41 Molecular Spreadsheet MDL Mol file conversion

save 39 save as 20 save in a database 174 selecting 61 split 121 type 134 writing files 33, 34 Molecule area default 54 naming conventions 207 rules 52 SYBYL object definition 198

27

Metal built-in set

43

210

211

Neutral global set 219 New SYBYL session 189 Non-bonded list 149 Normal

142

Notebook COLLECT command 191 PHOTO command 194


Read molecule 33 fragment library

O

16

O/S utilities dbtranslate see UNITY manuals use in MDL Mol conversion 43 dbunlock 166

Read/save database molecules 178

Object definitions 198

Recover contents of molecule area

Open saved SYBYL session

189

Reflect atoms 132

34 Open molecule file 33

Remove all atom attribute 121 all bond attribute 127 atom 121 bond 126 bond attributes 127 center of mass 139 centroid 139 extension point 140 global set 218 line 141 local set 221 non query atoms 145 normal 142 plane 143 stereo atom attribute 132 stereo bond attribute 132 substructure 129 UNITY feature 146

Operator difference 171, 211 grouping 213 intersection 171, 211 negation 171, 211 precedence 171 union 171, 211

P 193 Pen up 112 PHOTO 191, 194 Plane 143 Pause

measure angle 150 reflect through 132 Play back session COLLECT and TAKE files command file 192

219

Possible_hbond built-in set 225 PRO RS isomerism 130

219

Q Query expressions

170

QUICKBOND command

144 Replace chain 119, 128 Reset the screen 89 RENUMBER

Restore SYBYL session 189

Retrieve molecules

219

Pyrimidine global set

191

Restore from stack undo the last operation

Printing 156 Purine global set

125

R 118


94

169

Ring built-in set 225 fusion 134 list 155 ring fusion tutorial 103 SYBYL object definition RNA global set Root atom

Rawatom, adding

94

References chirality assignment 130 SHAKE algorithm 136

Open file dialog

Polar global set

Recording COLLECT command 191 PHOTO command 194

200

219

134

Rotation of molecules

17

SYBYL-X 1.1

RS isomerism

130

keyboard 32 menubar 27 mouse 27

S Save as molecules

Sidechain built-in set

39

SAVE_SESSION_DIR

184

Saving molecule in a file 33 formats 39 molecules 39 in a database 174 select molecule(s) 39 sketch 102 SYBYL session 184 Scanning torsions

136

SD file read/write files

226 Single bond 205 Sketcher 111 add Z coordinate 114 branching 113 change atom types 112 check chirality 101 draw a ring 114 draw multiple bonds 113 move an atom 116 save 102 techniques 111 toolbar items 115 tutorial 96 SLN read/write file

42

Search database

123

170 Select objects 61

SLN typer

Sequence built-in set

Sphere built-in set

Small molecule building (see SKETCH) 111

226

135 Split molecule 121 Standard amino acids global set 219

183 Session 183 delete 189 new 189 SESSION

Starting SYBYL

open saved session restore 189 save 184

189

215 aggregates 216 built-in 223 database 175 dynamic 222 for biopolymers 218 global 217 local 220 naming conventions 207 static 228 SYBYL object definition 201 user-defined 216 working with 229

SHAKED command Shortcuts dialogs

227

Spiro fusion

Sequence expression dialog 67

Sets

42

135

13, 25 Static set 228 define 228 SYBYL object definition

201

Store molecules 174 Subst_sphere built-in set

227

Substructure expression rules 206 modify 129 naming conventions 206 remove 129 root 129 selecting 61 SYBYL object definition 198 type 130 Substructure expression dialog 67 Sugar global set

219

27

SYBYL-X 1.1


in a database 171 in object expression

T TABLE DATABASE TAKE

172

192

Tear-off menus

26

TMPDIR environment variable To_atoms built-in set

177

227

Toolbar overview

UNITY defining features 145 MDL Mol file conversion to hitlist 43 modify feature 146 remove features and constraints 146 non query atoms 145 User-defined sets

29 Topography 149

211

216

Z

Torsion list angle 149 measure 148 modify 127

ZAP 89 ZE isomerism

130

Translate options 46 Translate molecular formats Translation of molecules Triple bond

44

17

205

21 TTY command 193 Tripos Bookshelf

Tutorials atom selection 75 bond selection 82 building a small molecule 96 file format 193 interacting with SYBYL 13 ring fusion 103 sketching a small molecule 96 small molecule sketching 96 substructure selection 85

U UIMS2 variables angle 148 collect file 192 database name 167, distance 148 height 148 photo file 195 plane angle 150 torsion 148 Undo last action

168

94

Union operator


SYBYL-X 1.1