automatically a molecular dictionary for use in FRODO/. TOM for any new group. The program requires only three character names and Cartesian coordinates ...
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Computer Programs J. Appl. Crvst. (I 99 I). 24, 405-406
F R D I C T - a computer program to generate a molecular dictionary for use in FRODOITOM. By V. PRASAD and MADHUSOODAN V. HOSUR,* Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Bombay 400 085, India
(Received 3 October !990; accepted 12 December 1990)
Abstract A computer program has been developed to generate automatically a molecular dictionary for use in FRODO/ TOM for any new group. The program requires only three character names and Cartesian coordinates for the atoms of the new group.
The crystallographic problem The three-dimensional structure of proteins determined by X-ray crystallography forms the basis for rational design of new molecules and the interactive computer graphics program FRODO (Jones, 1978) can be used effectively in this process. FRODO/TOM can be used to compose drug molecules ab initio from molecular fragments. An important feature of FRODO is its REFI option, in which molecular fragments distorted to fit into electron density maps or while achieving desired interactions with other molecules are ultimately refined (Hermans & McQueen, 1974) to their proper stereochemistry defined in a dictionary file. This dictionary file is an ordered atom list of the molecule, along with a list matrix whose structure has been described by Hermans & Ferro (1971). The list matrix specifies (i) atom connectivity, (ii) molecular stereochemistry and (iii) a key KI which denotes whether or not a particular dihedral angle is constrained. Molecular dictionaries have so far been prepared manually and this could, at times, become cumbersome. Here we describe a procedure and a computer program that will automatically generate such a dictionary given only atomic coordinates of the molecule. A computer program to make molecular dictionaries usable in a restrained least-squares refinement package (PROTIN/PROLSQ) has been reported recently (Pahler & Hendrickson, 1990).
Method of solution FRDICT requires the following free-format input with each data item being read from a new line; we have given in brackets the entries made for the heme group chosen here as an illustration: (a) a four-character alphanumeric name for the group whose dictionary is to be prepared (HEME); (b) number of atoms, N, in the group (42); (c) name of the data file containing atom names and their Cartesian coordinates (HEME:XYZ); * Author for correspondence. 0021-8898/91/040405-02503.00
(d) the format for reading atom names and coordinates (A3, 9X, 3F10.4); (e) window limits for bond distances in ,~, (1-1, 1.65). It is required that the first atom in the input list be bonded to only one other atom.t After reading a threecharacter name and three Cartesian coordinates for each atom, the program calculates interatomic distances to decide on bonded atoms. This covalent connectivity is stored in a matrix [(MAT(I,J), I = 1,N), J = I,N], a value of 1 for the IJ 'h element denoting connectivity between atoms I and J. With this connectivity information, the atoms are arranged in such a way that all atoms bonded to a particular atom are listed together. Among these atoms the ordering is done so as to place last that atom which has a forward chain emanating from it. If there are more atoms with forward chains, the atom which comes first in the input list is placed last. The program automatically finds out if a ring structure is encountered in the molecule and introduces dummy-atom pairs at appropriate positions. The program also suggests from a stereochemical viewpoint which dihedral angles are constrained and which are variable and makes entries of 0 or 1, respectively, for the corresponding KI keys (Hermans & Ferro, 1971) in the dictionary. This suggestion can be overridden by editing the dictionary file produced, if needed. We have given in Table 1 the dictionary file produced by our program for the fiat heme group shown in Fig. 1.
Software and hardware environment, program specification and availability The program has been written in standard Fortran 77 and does not use either overlay structure or any special library program. The dictionary produced by FRDICT has been succesfuily used with FRODO installed on a VG 3400 graphics system controlled by a PDPI 1/34 running under the R S X I l M operating system as well as with TOM (version 2.4) installed on Silicon Graphics IRIS 3100 and IRIS 4D work stations. Copies of the source code can be obtained from Dr M. V. Hosur. We thank Drs R. Chidambaram and K. K. Kannan for many stimulating discussions. Our thanks are due to the staff of Computer Division, BARC, for their constant help. 1 One way of dealing with ring structures would be to include a fictitious atom bonded to any one atom of the molecule. © 1991 International Union of Crystallography
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COMPUTER PROGRAMS T a b l e 1. Dictionary as prepared by F R D I C T
Atom names with an X at the end are dummy atoms introduced for purposes of ring closure. HEME CMI C31 C41 C21 CAI CII CH4 NI CIIX NIX CH1 CBI C14 C42 N4 C24 N2 C32 CM4 C34 C44 C22 C3M C!2 C34X CH3 C44X CA4 C I2X CA2 C22X CH2 CI 3 CB4 CB2 C43 N3 C23 CC4 N3X
I-1 2 0 2 1430 22870 22650 1 412 0 1 411 0 I 313 0 1 3900 0 8 0 0 0 6 0 0 1 614 0 05000 2 71615 2111817 11321 0 2132019 11424 0 2142322 016 0 0 11628 0 11526 0 11830 0 018 0 0 11732 0 021 0 0 12133 0 020 0 0 12034 0 022 0 0 12235 0 024 0 0 12436 0 2263837 12839 0 030 0 0 13241 0 13344 0 13343 0 2344645 036 0 0
52 0
1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 1 0 0 0 0 1 0
0.00 1.50 1.45 1-32 i .49 1.46 1.34 1.34 1.37 1.37 1-38 1.33 1.36 1.37 1.32 1.47 1.34 1.46 1.48 1.36 1-39 i .34 i.51 1.38 1.46 1.37 1-46 1-51 .45 .51 -45 .39 -39 .47 .33 -37 1-38 1.45 1.58 1.34
0 0 0 0 126 180 125 0 127 176 106 180 129 180 109 180 108 0 109 - 1 7 6 123 176 121 - 1 8 0 130 180 126 180 124 180 126 180 124 180 126 180 126 180 106 180 108 180 107 180 127 0 107 180 108 180 126 180 107 180 25 180 07 180 26 180 09 176 27 180 26 0 108 0 120 0 126 7 127 180 124 180 108 180 124 180
Table 1 (cont.) C33 C33X CA3 C43X 024 OI4 C23X CM3 CB3 CC3 023 O13
13648 0 038 0 0 13849 0 037 0 0 039 0 0 039 0 0 041 0 0 041 0 0 14350 0 2495251 050 0 0 050 0 0
0 0 I 0 0 0 0 0 I 1 0 0
1"46 1.34 1.51 1.34 1"25 1.17 1.34 1.51 i.50 1.54 1.19 1.24
126 107 127 107 !i9 121 107 127 108 108 121 117
180 180 0 180 180 0 180 0 0 180 180 0
I CM1
O14
~A4 ~ C 4 4 4
NC:4
N1~1
CB1
/.1 "~O23 ~
\____ /C13
i
\N3
CM3
1--
~--
~"~ CB2
Fig. i. Atom-numbering scheme for the flat heme group input to
FRDICT. References
HERMANS, J. JR & FERRO, D. (1971). Biopolymers, 10, 1121-1138. HERMANS, J. JR & MCQUEEN, J. E. JR (1974). Acta Cryst. A30, 730-739. JONES, T. A. (1978). J. Appl. Cryst. I I, 268-272. PAHLER, A. & HENDRICKSON, W. A. (1990). J. Appl. Cryst. 23, 218-221.
Laboratory Notes J. Appl. Cryst. ( 1991 ). 24, 406-408
Protein crystal growth in the presence of poly(vinylidene difluoride) membrane. By JOHN S. PUNZI,* Biotechnology Research Services, 27 Debran Drive, Henrietta, New York 14467, USA, a n d JOSEPH LUFT a n d VlVlAN CODY, Department of Molecular Biophysics, Medical Foundation of Buffalo, 73 High Street, Buffalo, New York 14203,
USA (Received 10 December 1990; accepted 29 January 1991 ) Crystallization o f m a c r o m o l e c u l e s is usually a c c o m p l i s h e d by a trial-and-error process that frequently c o n s u m e s large a m o u n t s o f protein. All m e t h o d s e m p l o y e d for p r o t e i n crystal f o r m a t i o n rely on a limited a m o u n t o f s u p e r s a t u * Author to whom correspondence should be addressed. 0021-8898/91/040406-03503.00
r a t i o n o f the p r o t e i n which results in the f o r m a t i o n o f an a g g r e g a t e followed by n u c l e a t i o n a n d s u b s e q u e n t crystal g r o w t h . If m e t h o d s can be d e v e l o p e d to p r o m o t e limited a g g r e g a t i o n or nucleation, then p r o t e i n crystals can be g r o w n f r o m substantially lower p r o t e i n c o n c e n t r a t i o n s t h a n presently used. Alternatively, proteins which are © 1991 I n t e r n a t i o n a l U n i o n o f C r y s t a l l o g r a p h y
