Free energy, entropy and heat capacity of the hydrophobic interaction as afunction of pressure

Molecular dynamics simulations of a methane pair in water are used to calcu late the thermodynamic properties of the hydrophobic interaction as a funct ion of pressure. Pressure is found to decrease the tendency to form methane aggregates. The entropic contribution to the free energy, which at atmosph eric pressure greatly stabilizes aggregation, is highly pressure dependent. As the pressure increases, the entropic stabilization steadily decreases u ntil, at 7 kbar, the entropy of the contact pair is equal to the entropy of the solvent separated pair. The heat capacity change between the contact a nd solvent separated Fair is shown to be large and positive at 1 atm, as is characteristic of hydrophobic processes. At higher pressures, the heat cap acity change is zero, indicating that two of the significant properties of the hydrophobic effect, the large entropy decrease and heat capacity increa se are lost at high pressures. The free energy, volume and entropy changes are consistent with the corresponding changes for the pressure denaturation of proteins.