New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

摘要

Solvation free energy is a fundamental thermodynamic quantity that should be determined to estimate various physicochemical properties of a molecule and the desolvation cost for its binding to macromolecular receptors. Here, we propose a new solvation free energy function through the improvement of the solvent-contact model, and test its applicability in estimating the solvation free energies of organic molecules with varying sizes and shapes. This new solvation free energy function is constructed by combining the existing solute-solvent interaction term with the self-solvation term that reflects the effects of intramolecular interactions on solvation. Four kinds of atomic parameters should be determined in this solvation model: atomic fragmental volume, maximum atomic occupancy, atomic solvation, and atomic self-solvation parameters. All of these parameters for total 37 atom types are optimized by the operation of a standard genetic algorithm in such a way to minimize the difference between the experimental solvation free energies and those calculated by the solvation free energy function for 362 organic molecules. The solvation free energies estimated from the new solvation model compare well with the experimental results with the associated squared correlation coefficients of 0.88 and 0.85 for training and test sets, respectively. The present solvation model is thus expected to be useful for estimating the solvation free energies of organic molecules.