A Generalized Kirkwood Implicit Solvent for the Polarizable AMOEBA Protein Model

Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding calculations, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but use of explicit solvent can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of interstitial space corrections to account for biomolecular geometry. These corrections include updating pairwise descreening scale factors to be element-specific and adding neck and tanh corrections to the calculation of effective radii. We then apply the AMOEBA/GK implicit solvent to a set of nine proteins and achieve an average RMSD of 2.1 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help to facilitate simulation of arbitrary biomolecules on biologically relevant timescales.