Potentials of Mean Force for the Interaction of Blocked Alanine Dipeptide Molecules in Water and Gas Phase from MD Simulations

We calculate potentials of mean force (PMFs) for the intermolecular interaction of two blocked alanine dipeptide (AcAlaNHMe) molecules in water and gas phase at two temperatures, 278 and 300 K, from all-atom molecular dynamics simulations. Simple models based on buried solvent accessible surface and one-dimensional potentials derived from distance-based radial distribution functions are not capable of expressing the short- and long-range complexity of the solute-solute interactions in water. Instead, radial and angular variations in the PMFs are observed with the two-dimensional potentials. The strength of the interactions for specific relative orientations of the molecules in the two-dimensional PMFs is more than double that observed in the one-dimensional PMFs. The populations of specific blocked alanine dipeptide conformations in water, such as αR and PPII, vary with temperature, and most significantly, with the distance between the centers of mass. A preference for helical conformations is observed at close encounter between molecules.