Screened coulomb potential based implicit solvent model: Formulation and parameter development

Abstract

An implicit solvent model (ISM) for use in molecular mechanics, Monte Carlo, and molecular dynamics simulations on proteins and nucleic acids is proposed that is based on describing the electrostatic component with a screened Coulomb potential (SCP). The SCP has been extended so that both the electrostatic interaction energies and the self-energy terms are included in the solvation energy where the latter has been calculated from the integral Born equation. In addition, the SCP is generalized to allow an accounting of the positional dependence of the interactions between charges in a dielectric. To test the potential of the method to provide a reliable and fast implicit description of solvent, a parameter set has been determined to calculate hydration free energies of a group of small-molecule analogs for neutral amino acid residues. Comparison of the calculated with experimental hydration energies of 18 molecules yields a correlation greater than 0.99, demonstrating the feasibility of the method to form the basis of an ISM. A parameter set based solely on hydration energies is not sufficient to account for the considerably different physical conditions found for a solute in the protein "solvent." Methods are explored for further generalizing the parameters to account for macromolecular structure, and it is shown that it may be possible to find a positional function of the coordinates that correlates well with the fraction of each amino acid residue buried in the macromolecule. Such a function would reduce computing time by replacing the need for repetitive calculations of the solvent-accessible surface area (and its derivatives in the case of molecular dynamics simulations) with a simple function of the coordinates. © 1998 John Wiley & Sons, Inc.