Extended solvent-contact model for protein solvation: Test cases for dipeptides

• We proposed a solvation free energy function for proteins comprising solvation and self-solvation terms.
• Solvation free energies of dipeptides estimated with this energy function compared well with quantum mechanical results.
• The accuracy of solvation free energy function was enhanced significantly by the addition of the self-solvation term.

Solvation effects are critically important in the structural stabilization and functional optimization of proteins. Here, we propose a new solvation free energy function for proteins, and test its applicability in predicting the solvation free energies of dipeptides. The present solvation model involves the improvement of the previous solvent-contact model assuming that the molecular solvation free energy could be given by the sum over the individual atomic contributions. In addition to the existing solvent-contact term, the modified solvation free energy function includes the self-solvation term that reflects the effects of intramolecular interactions in the solute molecule on solute–solvent interactions. 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 16 atom types are optimized with a standard genetic algorithm in such a way to minimize the difference between the solvation free energies of dipeptides obtained from high-level quantum chemical calculations and those predicted by the solvation free energy function. The solvation free energies of dipeptides estimated from the new solvation model are in good agreement with the quantum chemical results. Therefore, the optimized solvation free energy function is expected to be useful for examining the structural and energetic features of proteins in aqueous solution.

We propose a new solvation free energy function for proteins comprising intermolecular solvation and intramolecular self-solvation terms.Figure optionsDownload high-quality image (79 K)Download as PowerPoint slide