HYDRATION AND CONFORMATIONAL EQUILIBRIA OF SIMPLE HYDROPHOBIC AND AMPHIPHILIC SOLUTES

We consider whether the continuum model of hydration optimized to repr oduce vacuum-to-water transfer free energies simultaneously describes the hydration free energy contributions to conformational equilibria o f the same solutes in water. To this end, transfer and conformational free energies of idealized hydrophobic and amphiphilic solutes in wate r are calculated from explicit water simulations and compared to conti nuum model predictions. As benchmark hydrophobic solutes, we examine t he hydration of linear alkanes from methane through hexane. Amphiphili c solutes were created by adding a charge of +/-1e to a terminal methy l group of butane. We find that phenomenological continuum parameters fit to transfer free energies are significantly different from those f it to conformational free energies of our model solutes. This differen ce is attributed to continuum model parameters that depend on solute c onformation in water, and leads to effective values for the free energ y/surface area coefficient and Born radii that best describe conformat ional equilibrium. In light of these results, we believe that continuu m models of hydration optimized to fit transfer free energies do not a ccurately capture the balance between hydrophobic and electrostatic co ntributions that determines the solute conformational state in aqueous solution.