Hydrophobic interactions between methane and a nanoscopic pocket: three dimensional distribution of potential of mean force revealed by computer simulations

We consider a model system of methane molecule and a hemispherical, hydrophobic pocket of an 8 A radius, remaining together in aqueous environment. A spatial map of potential of mean force acting on methane molecule due to presence of pocket is constructed, based on a series of explicit solvent molecular dynamics simulations. A relation between free energy variations associated with methane translocations and accompanying changes in solvent density distribution is analyzed. A funnel-like area where free energy is diminished with respect to bulk is present over the pocket entrance and extends up to 9 A toward the bulk solvent. In order to get into the pocket, however, methane has to cross a free energy barrier, which is more prominent around the circumferential part of pocket entrance, while achieving bulklike free energy values at the very center. As a methane molecule crosses this barrier, the pocket gets completely dehydrated, which leads to "hydrophobic collapse," manifested by a sharp decrease in free energy. We find that the observed free energy changes are closely related to interactions between the methane hydration shell and the surrounding solvent. Results presented here are a continuation of our previous studies of methane-pocket systems.