Pressure Correction for Solvation Theories

TL;DR

This paper introduces a simple correction method for solvation theories that improves the accuracy of hydration free energy predictions for small molecules, matching long molecular simulations in seconds.

Contribution

It proposes an optimized Van der Waals volume correction to address pressure overestimation in liquid state theories, enhancing their predictive accuracy.

Findings

Corrected theories accurately predict hydration free energies.

The correction is computationally efficient, taking seconds.

Improves upon uncorrected solvation models in accuracy.

Abstract

Liquid state theories such as integral equations and classical density functional theory often overestimate the bulk pressure of fluids because they require closure relations or truncations of functionals. Consequently, the cost to create a molecular cavity in the fluid is no longer negligible and those theories predict wrong solvation free energies. We show how to correct them simply by computing an optimized Van der Walls volume of the solute and removing the undue free energy to create such volume in the fluid. Given this versatile correction, we demonstrate that state-of-the-art solvation theories can predict, within seconds, hydration free energies of a benchmark of small neutral drug-like molecules with the same accuracy as day-long molecular simulations.