The impact of surface area, volume, curvature and Lennard-Jones potential to solvation modeling

TL;DR

This study investigates how surface area, volume, curvature, and Lennard-Jones potential influence solvation free energy predictions, highlighting the importance of curvature and LJ potential in nonpolar solvation models.

Contribution

It introduces new curvature-based nonpolar solvation models and demonstrates the critical role of Lennard-Jones potential in improving prediction accuracy.

Findings

Surface area and volume are highly correlated.

Curvatures are weakly correlated with surface area and volume.

Lennard-Jones potential significantly enhances solvation modeling accuracy.

Abstract

This paper explores the impact of surface area, volume, curvature and Lennard-Jones potential on solvation free energy predictions. Rigidity surfaces are utilized to generate robust analytical expressions for maximum, minimum, mean and Gaussian curvatures of solvent-solute interfaces, and define a generalized Poisson-Boltzmann (GPB) equation with a smooth dielectric profile. Extensive correlation analysis is performed to examine the linear dependence of surface area, surface enclosed volume, maximum curvature, minimum curvature, mean curvature and Gaussian curvature for solvation modeling. It is found that surface area and surfaces enclosed volumes are highly correlated to each others, and poorly correlated to various curvatures for six test sets of molecules. Different curvatures are weakly correlated to each other for six test sets of molecules, but are strongly correlated to each other within each test set of molecules. Based on correlation analysis, we construct twenty six nontrivial nonpolar solvation models. Our numerical results reveal that the Lennard-Jones (LJ) potential plays a vital role in nonpolar solvation modeling, especially for molecules involving strong van der Waals interactions. It is found that curvatures are at least as important as surface area or surface enclosed volume in nonpolar solvation modeling. In conjugation with the GPB model, various curvature based nonpolar solvation models are shown to offer some of the best solvation free energy predictions for a wide range of test sets. For example, root mean square errors from a model constituting surface area, volume, mean curvature and LJ potential are less than 0.42 kcal/mol for all test sets.