Implicit Solvation Using the Superposition Approximation (IS-SPA): Extension to Peptides in a Polar Solvent.

Abstract

Efficient, accurate, and adaptable implicit solvent models remain a significant challenge in the field of molecular simulation. A recent implicit solvent model, IS-SPA, based on approximating the mean solvent force using the superposition approximation, provides a platform to achieve these goals. IS-SPA was originally developed to handle nonpolar solutes in a polar solvent and did not accurately capture polar solvation. Here, we demonstrate that IS-SPA can accurately capture polar solvation by incorporating solvent orientation and accounting for the contributions from long ranged electrostatics. Solvent orientation is approximated as that of an ideal dipole aligned in a mean electrostatic field and an analytic form of the long ranged electrostatics is derived. Parameters for the model are calculated from explicit solvent simulations of an isolated atom or molecule and include atom-based solvent densities, mean electric field functions, radially symmetric averaged Lennard-Jones forces, and multipoles of the explicit solvent model. Using these parameters, IS-SPA accounts for asymmetry of charge solvation and reproduces the explicit solvent potential of mean force of dimerization of two oppositely charged Lennard-Jones spheres in chloroform with high fidelity. Additionally, the model more accurately captures the effect of explicit solvent on the monomer and dimer configurations of alanine dipeptide in chloroform than a generalized Born or constant density dielectric model. The current version of the algorithm is expected to outperform explicit solvent simulations for aggregation of small peptides at concentrations below 150 mM, well above the typical experimental concentrations for these materials.