Molecular dynamics simulations of pressure effects on hydrophobic interactions

We report results on the pressure effects on hydrophobic interactions obtai ned from molecular dynamics simulations of aqueous solutions of methanes in water. A wide range of pressures that is relevant to pressure denaturation of proteins is investigated. The characteristic features of water-mediated interactions between hydrophobic solutes are found to be pressure-dependen t. In particular, with increasing pressure we find that (1) the solvent-sep arated configurations in the solute-solute potential of mean force (PMF) ar e stabilized with respect to the contact configurations; (2) the desolvatio n barrier increases monotonically with respect to both contact and solvent- separated configurations; (3) the locations of the minima and the barrier m ove toward shorter separations; and (4) pressure effects are considerably a mplified for larger hydrophobic solutes. Together, these observations lend strong support to the picture of the pressure denaturation process proposed previously by Hummer et al. (Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1552) : with increasing pressure, the transfer of water into protein interior bec omes key to the pressure denaturation process, leading to-the dissociation of close hydrophobic contacts and subsequent swelling of the hydrophobic pr otein interior through insertions of water molecules. The pressure dependen ce of the PMF between larger hydrophobic solutes shows that pressure effect s on the interaction between hydrophobic amino acids may be considerably am plified compared to those on the methane-methane PMF.