Variational approach for nonpolar solvation analysis.

Solvation analysis is one of the most important tasks in chemical and biological modeling. Implicit solvent models are some of the most popular approaches. However, commonly used implicit solvent models rely on unphysical definitions of solvent-solute boundaries. Based on differential geometry, the present work defines the solvent-solute boundary via the variation of the nonpolar solvation free energy. The solvation free energy functional of the system is constructed based on a continuum description of the solvent and the discrete description of the solute, which are dynamically coupled by the solvent-solute boundaries via van der Waals interactions. The first variation of the energy functional gives rise to the governing Laplace-Beltrami equation. The present model predictions of the nonpolar solvation energies are in an excellent agreement with experimental data, which supports the validity of the proposed nonpolar solvation model.