AN EVALUATION OF IMPLICIT AND EXPLICIT SOLVENT MODEL SYSTEMS FOR THE MOLECULAR-DYNAMICS SIMULATION OF BACTERIOPHAGE-T4 LYSOZYME

In this report we examine several solvent models for use in molecular dynamics simulations of protein molecules with the Discover program fr om Biosym Technologies. Our goal was to find a solvent system which st rikes a reasonable balance among theoretical rigor, computational effi ciency, and experimental reality. We chose phage T4 lysozyme as our mo del protein and analyzed 14 simulations using different solvent models . We tested both implicit and explicit solvent models using either a l inear distance-dependent dielectric or a constant dielectric. Use of a linear distance-dependent dielectric with implicit solvent significan tly diminished atomic fluctuations in the protein and kept the protein close to the starting crystal structure. In systems using a constant dielectric and explicit solvent, atomic fluctuations were much greater and the protein was able to sample a larger portion of conformational space. A series of nonbonded cutoff distances (9.0, 11.5, 15.0, 20.0 Angstrom) using both abrupt and smooth truncation of the nonbonded cut off distances were tested. The method of dual cutoffs was also tested. We found that a minimum nonbonded cutoff distance of 15.0 Angstrom wa s needed in order to properly couple solvent and solute. Distances sho rter than 15.0 Angstrom resulted in a significant temperature gradient between the solvent and solute. In all trajectories using the proprie tary Discover switching function, we found significant denaturation in the protein backbone; we were able to run successful trajectories onl y in those simulations that used no switching function. We were able t o significantly reduce the computational burden by using dual cutoffs and still calculate a quality trajectory. In this method, we found tha t an outer cutoff distance of 15.0 Angstrom and an inner cutoff distan ce of 11.5 worked well. While a 10 Angstrom shell of explicit water yi elded the best results, a 6 Angstrom shell of water yielded satisfacto ry results with nearly a 40% reduction in computational cost. (C) 1994 Wiley-Liss, Inc.