(223l) Direct Evaluation of Polypeptide Partial Molar Volumes in Water Using Molecular Dynamics Simulations

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, providing an insight into the properties of oligopeptides and proteins in the idealized random coil reference state. For the zwitterionic terminated chains, however, simulations exhibit a constant, lower volume than experiment, suggesting simulations over predict electrostriction by the charged end groups. The simulation volumes are well described by a group contribution correlation, yielding excellent agreement between simulated side chain group volumes and experiment. The accuracy of our simulations and fidelity of the group additivity model to reproduce simulation volumes suggest it is possible to screen the potential effects of side chain interactions on group volumes when they are charged and more significantly influence neighboring hydration shells.