Implicit treatment of solvent dispersion forces in protein simulations

Abstract

A model is proposed for the evaluation of dispersive forces in a continuum solvent representation for use in large-scale computer simulations. The model captures the short- and long-range effects of water-exclusion in conditions of partial and anisotropic hydration. The model introduces three parameters, one of which represents the degree of hydration (water occupancy) at any point in the system, which depends on the solute conformation, and two that represent the strength of water-water and water-solute dispersive interactions. The model is optimized for proteins, using hydration data of a suboptimally hydrated binding site and results from dynamics simulations in explicit water. The model is applied to a series of aliphatic-alcohol/protein complexes and a set of binary and ternary complexes of various sizes. Implications for weak and ultra-weak protein-protein association and for simulation in crowded media are discussed. © 2014 Wiley Periodicals, Inc.