Modeling molecular and ionic absolute solvation free energies with quasi-chemical theory bounds

TL;DR

This paper introduces efficient Bayesian and bounding methods within quasi-chemical theory to accurately compute molecular and ionic solvation free energies, demonstrated on various aqueous solutes.

Contribution

It develops new computational techniques for partitioning and estimating solvation free energies using bounds and Bayesian methods within QCT.

Findings

Accurate solvation free energies for multiple solutes.

Near-Gaussian energy distributions enable efficient bounds.

Methods outperform traditional approaches in accuracy and efficiency.

Abstract

A recently developed statistical mechanical Quasi-Chemical Theory (QCT) has led to significant insights into solvation phenomena for both hydrophilic and hydrophobic solutes. The QCT exactly partitions solvation free energies into three components: 1) inner-shell chemical, 2) outer-shell packing, and 3) outer-shell long-ranged contributions. In this paper, we discuss efficient methods for computing each of the three parts of the free energy. A Bayesian estimation approach is developed to compute the inner-shell chemical and outer-shell packing contributions. We derive upper and lower bounds on the outer-shell long-ranged portion of the free energy by expressing this component in two equivalent ways. Local, high energy contacts between solute and solvent are eliminated by spatial conditioning in this free energy piece, leading to near-Gaussian distributions of solute-solvent interactions energies. Thus, the average of the two mean-field bounds yields an accurate and efficient free energy estimate. Aqueous solvation free energy results are presented for several solutes, including methane, perfluoromethane, water, and the sodium and chloride ions. The results demonstrate the accuracy and efficiency of the methods. The approach should prove useful in computing solvation free energies in inhomogeneous, restricted environments.