Direct Evaluation of Polypeptide Partial Molar Volumes in Water Using Molecular Dynamics Simulations

Abstract

Molecular simulations of a series of tri- and tetrapeptides with the sequences Gly-X-Gly and Gly-X-Y-Gly, where X and Y are neutral amino acid side chains, have been performed to characterize their volumetric properties in water at 300 K. The chains were terminated with both zwitterionic and neutral N-acetyl/amide functionalities to examine end group effects. The simulations accurately capture the experimental effects of side chain mutations and increasing peptide length, suggesting simulations can provide insight into the properties of unfolded oligopeptides and proteins. For the zwitterionic terminated chains, however, simulations exhibit a constant, lower volume than the experiment, suggesting that simulations over-predict electrostriction by the charged end groups. The simulation volumes are well-described by a group additivity based correlation, yielding excellent agreement between simulated side chain group volumes and the experiment. The accuracy of our simulations and fidelity of the group additiv...