MOLECULAR-DYNAMICS SIMULATION WITH A CONTINUUM ELECTROSTATIC MODEL OFTHE SOLVENT

The accuracy and simplicity of the Poisson-Boltzmann electrostatics mo del has led to the suggestion that it might offer an efficient solvent model for use in molecular mechanics calculations on biomolecules. We report a successful merger of the Poisson-Boltzmann and molecular dyn amics approaches, with illustrative calculations on the small solutes dichloroethane and alanine dipeptide. The algorithm is implemented wit hin the program UHBD. Computational efficiency is achieved by the use of rather coarse finite difference grids to solve the Poisson-Boltzman n equation. Nonetheless, the conformational distributions generated by the new method agree well with reference distributions obtained as Bo ltzmann distributions from energies computed with fine finite differen ce grids. The conformational distributions also agree well with the re sults of experimental measurements and conformational analyses using m ore detailed solvent models. We project that when multigrid methods ar e used to solve the finite difference problem and the algorithm is imp lemented on a vector supercomputer, the computation of solvent electro static forces for a protein of modest size will add only about 0.1 s c omputer time per simulation step relative to a vacuum calculation. (C) 1995 by John Wiley & Sons, Inc.