A Generalized Kirkwood Implicit Solvent for the Polarizable AMOEBA Protein Model

Abstract

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.

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Minor edit.

Content

Supplementary material

Supplemental Information
The supplemental information contains 1) parameters for computing neck corrections to pairwise descreening interactions and 2) base generalized Kirkwood radii used to define the solute-solvent boundary.

Supplementary weblinks

Force Field X Home Page
Force Field X is an atomic resolution molecular modeling application that targets open research questions in the areas of: 1) Predicting the structure, thermodynamic stability and solubility of organic polymer crystals. 2) Predicting the effect of missense mutations on protein structure, thermodynamics and molecular phenotype. 3) Computational design of biomolecules in both soluble and crystalline environments.
Force Field X Github
The source code for the "Generalized Kirkwood Implicit Solvent for the Polarizable AMOEBA Protein Model" is available within Force Field X.