Implementing Advanced Force Fields for Simulation of Physical and Biological Processes Tom Darden1 , Andres Cisneros, Jean-Philip Piquemal, and Denny Elking2 1
2
National Institutes of Health NIEHS, Res Tri Pk NC 27709, USA,
[email protected], WWW home page: http://dir.niehs.nih.gov/dirlsb/cchome.htm Complex Carbohydrate Research Center University of Georgia, Athens GA 30602-4712, USA
Abstract. The abstract should summarize the contents of the paper using at least 70 and at most 150 words. It will be set in 9-point font size and be inset 1.0 cm from the right and left margins. There will be two blank lines before and after the Abstract. . . .
1
Introduction
Molecular dynamics (MD) is a way to simulate at an atomic scale the structure and motion of macromolecules such as proteins, together with their environment including solvent, counterions, relevant ligands and other pertinent molecules. MD treats the atomic nuclei as classical particles subject to interatomic forces given ideally by the Born-Oppenheimer approximation to the Schrodinger equation, but practically by empirically fitted force fields. In principle MD provides a fully detailed picture of biophysical events, able to supplement the information provided by experimental techniques such as X-ray crystallography and NMR spectroscopy. In practice it is limited by the competing requirements of sufficient sampling and sufficient accuracy. That is, current protein simulations are limited (by available computer power) to the multi-nanosecond time scale (in specific cases MD has been able to reach the microsecond timescale), whereas the relevant biophysical timescale is millisecond to second. Thus a focus of much current research is on ways to accelerate MD to the relevant timescales. On the other hand, current simulation lengths together with sophisticated free energy estimators are already sufficient to demonstrate that current macromolecular force fields have serious shortcomings [1]. Thus another active area of research is the exploration of ways to improve force fields. My talk focuses on our group’s efforts towards the latter goal. Most current macromolecular force fields have the following (class I) form for energy E as a function of system conformation RN : E(RN ) =
X
bonds
Kb (b − beq )2 +
X
angles
Ka (θ − θeq )2
2
# " X Aij Bij qi qj Vn (1 + cos(nφ − γ)) + + 12 − R6 + ²R 2 Rij ij ij i
