Water properties and potential of mean force for hydrophobic interactions of methane and nanoscopic pockets studied by computer simulations

We consider model systems consisting of a methane molecule and hemispherical pockets of subnanometer radii whose walls are made of hydrophobic material. The potential of mean force for process of translocation of the methane molecule from bulk water into the pockets' interior is obtained, based on an explicit solvent molecular dynamics simulations. Accompanying changes in water density around the interacting objects and spatial distribution of solvent's potential energy are analyzed, allowing for interpretation of details of hydrophobic interactions in relation to hydrophobic hydration properties. Applicability of surface area-based models of hydrophobic effect for systems of interest is also investigated. A total work for the translocation process is not dependent on pocket's size, indicating that pocket desolvation has little contribution to free energy changes, which is consistent with the observation that solvent density is significantly reduced inside "unperturbed" pockets. Substantial solvent effects are shown to have a longer range than in case of a well investigated methane pair. A desolvation barrier is present in a smaller pocket system but disappears in the larger one, suggesting that a form of a "hydrophobic collapse" is observed.