Parametrized Model for Aqueous Free Energies of Solvation Using Geometry-Dependent Atomic Surface Tensions with Implicit Electrostatics

Abstract

We present a new model for predicting aqueous free energies of solvation based entirely on geometry-dependent atomic surface tensions. The model is especially suited for rapid estimations on large molecules or large sets of molecules. This method is designed to be employed with gas-phase geometries to obtain solvation free energies of organic molecules containing H, C, N, O, F, S, Cl, and Br. We parametrized the model by using a training set containing 235 neutral solutes with a variety of functional groups, and we achieve a mean unsigned error of 0.55 kcal/mol when the model is applied using gas-phase geometries calculated at the Hartree−Fock level with a heteroatom-polarized valence-double-zeta basis set (HF/MIDI!) and a mean unsigned error of 0.57 kcal/mol when it is applied using gas-phase geometries from Austin Model 1 (AM1). For a smaller set of 99 solutes, we compared the new model to two previously published models based on atomic solvation parameters, and we achieve a mean unsigned error of 0.56 kcal/mol as compared to 1.87 and 2.13 kcal/mol for the previous models. A simple extension is provided to allow treatment of certain kinds of charged groups. The model is expected to be especially useful for problems requiring high efficiency because of the size of the system, e.g., protein folding, or problems requiring rapid estimations because of the large number of calculations required, e.g., scoring of combinatorial libraries.