The non-polar solvent potential of mean force for the dimerization of alanine dipeptide: the role of solute-solvent van der Waals interactions

The non-polar component of the potential of mean force of dimerization of alanine dipeptide has been calculated in explicit solvent by free energy perturbation. We observe that the calculated PMF is inconsistent with a non-polar hydration free energy model based solely on the solute surface area. The non-linear behavior of the solute-solvent van der Waals energy is primarily responsible for the non-linear dependence of the potential of mean force with respect to the surface area. The calculated potential of mean force is reproduced by an implicit solvent model based on a solvent continuum model for the solute-solvent van der Waals interaction energy and the surface area for the work of forming the solute cavity.