(311c) Solvation Free Energy of Amino Acids and Side-Chain Analogs

Chang, J., University of Delaware

The solvation free energies of amino acids and their side-chain analogs in water and cyclohexane are calculated using Monte Carlo simulation. Molecular interactions are described by the OPLS-AA force field for the amino acids and the TIP4P model for water, and the free energies are determined using the Bennett acceptance method. Results for the side-chain analogs in cyclohexane and in water are used to evaluate the performance of the force field for the van der Waals and the electrostatic interactions, respectively. Comparison of the hydration free energies for the amino acid analogs and the full amino acids allows assessment of the additivity of the side chain contributions in hydrating water molecules. While the hydration free energies of neutral amino acids can be reasonably approximated by adding the contributions of the respective side chains to that of glycine, significant non-additivity in the free energy is found for the zwitterionic form of amino acids with polar side chains. In serine and threonine, intramolecular hydrogen bonds are formed between the polar side chains and backbone groups, leading to weaker solvation than for glycine. In contrast, such non-additivity is not observed in tyrosine, in which the hydroxyl group is farther separated from, and cannot form an intramolecular hydrogen bond with, the backbone. With histidine we find that a water molecule can form a bridge when the intramolecular hydrogen bond between the polar group and the backbone is broken.