I-SOLV: A new surface-based empirical model for computing solvation free energies

Abstract

We have developed a new empirical model, I-SOLV, for computing solvation free energies of neutral organic molecules. It computes the solvation free energy of a solute molecule by summing up the contributions from its component atoms. The contribution from a certain atom is determined by the solvent-accessible surface area as well as the surface tension of this atom. A total of 49 atom types are implemented in our model for classifying C, N, O, S, P, F, Cl, Br and I in common organic molecules. Their surface tensions are parameterized by using a data set of 532 neutral organic molecules with experimentally measured solvation free energies. A head-to-head comparison of our model with several other solvation models was performed on a test set of 82 molecules. Our model outperformed other solvation models, including widely used PB/SA and GB/SA models, with a mean unsigned error as low as 0.39 kcal/mol. Our study has demonstrated again that well-developed empirical solvation models are not necessarily less accurate than more sophisticated theoretical models. Empirical models may serve as appealing alternatives due to their simplicity and accuracy.