On the transferability of fractional contributions to the hydration free energy of amino acids

Abstract

AbstractThis study reports the application of the quantum mechanical self-consistent reaction field MST method to compute the solvation profile in water of the twenty natural amino acids. The aim is to derive intrinsic fractional contributions to the hydration free energy and to examine their transferability to peptides. To this end, IEFMST calculations have been performed at the B3LYP/6- 31G(d) level for the series of acetyl amino acid amides, which were chosen as model compounds. In order to account for the flexibility of both the backbone and the side chain in deriving the hydration fractional contributions, calculations have been performed for representative conformers taken from the Dunbrack’s backbone-dependent conformational library. The results allow us to dissect the hydration free energy into backbone and side chain contributions and examine the conformational dependence of the fragmental contributions to hydration. For the backbone, different hydration contributions are found for α-helical and β-sheet conformations, which mainly reflect differences in the electrostatic contribution to hydration of the carbonyl group. In contrast, the conformational flexibility of the side chain is found to have little impact on the fractional contribution to hydration. These findings should be valuable to refine semiempirical methods for predicting solvation properties of peptides and proteins in large-scale genomic studies.KeywordsHydration free energyContinuum solvation modelsAtomic solvation profileAmino acidsPeptides