MOLECULAR-DYNAMICS SIMULATION WITH A CONTINUUM ELECTROSTATIC MODEL OF THE SOLVENT

The accuracy and simplicity of the Poisson-Boltzmann electrostatics model 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 dynamics approaches, with illustrative calculations on the small solutes dichloroethane and alanine dipeptide. The algorithm is implemented within the program UHBD. Computational efficiency is achieved by the use of rather coarse finite difference grids to solve the Poisson-Boltzmann equation. Nonetheless, the conformational distributions generated by the new method agree well with reference distributions obtained as Boltzmann distributions from energies computed with fine finite difference grids. The conformational distributions also agree well with the results of experimental measurements and conformational analyses using more detailed solvent models. We project that when multigrid methods are used to solve the finite difference problem and the algorithm is implemented on a vector supercomputer, the computation of solvent electrostatic forces for a protein of modest size will add only about 0.1 s computer time per simulation step relative to a vacuum calculation. (C) 1995 by John Wiley & Sons, Inc.