Molecular Dynamics Simulations of Pressure Effects on Hydrophobic Interactions

Abstract

We report results on the pressure effects on hydrophobic interactions obtained 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-dependent. In particular, with increasing pressure we find that (1) the solvent-separated configurations in the solute-solute potential of mean force (PMF) are stabilized with respect to the contact configurations; (2) the desolvation barrier increases monotonically with respect to both contact and solvent-separated configurations; (3) the locations of the minima and the barrier move toward shorter separations; and (4) pressure effects are considerably amplified 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 becomes key to the pressure denaturation process, leading to the dissociation of close hydrophobic contacts and subsequent swelling of the hydrophobic protein interior through insertions of water molecules. The pressure dependence of the PMF between larger hydrophobic solutes shows that pressure effects on the interaction between hydrophobic amino acids may be considerably amplified compared to those on the methane-methane PMF.

Hydrophobic effect in the pressure-temperature plane

“…At fixed pressures it reaches its maximum, temperature of which is what we call T 2 , and then turns to decrease with increasing T; at fixed temperatures ͑below 350 K͒ it increases with increasing P, and the characteristic temperature T 2 decreases with increasing P. We note that W(1)/kT represents the solventmediated potential of mean force at the shortest possible distance in this model but may not correspond to the one at a contact pair in a real system; computer simulations of methane in water show that strength of solvent-mediated attraction increases with increasing pressure at solvent-separated configurations and at distances shorter than a crossover point around 3.9 Å. 20 The two characteristic temperatures, T 1 and T 2 , versus P are plotted in Fig. 8.…”

“…It is plotted in Fig. 7 as a function of T at the six pressures Pϭ0.1, 10,20,30,40, and 50 MPa. The strength of attraction as measured by ϪW(1)/kT shows dependences on temperature and on pressure similar to those of ex /kT.…”

“…There are numerous studies, both experimental and theoretical, on the hydrophobic effect so that even representative works cannot be cited here all. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Many of the theoretical studies are based on realistic models of water, 10,12,14,16 -22 some focusing on the origin of solubility minimum 14,16 and some addressing pressure effects on the hydrophobic interaction in connection with pressure denaturation of proteins. 13,18,20,21 We will calculate, with a lattice model to be described below, the characteristic temperatures of the hydrophobic hydration and the hydrophobic attraction as functions of pressure.…”

Temperature dependence of the hydrophobic hydration and interaction of simple solutes: An examination of five popular water models

“…As a consequence, with increasing temperature the association of hydrophobic particles is found to be enhanced in order to minimise the solvation entropy penalty [8,9]. This entropy-driven association process is usually referred to as hydrophobic interaction and has been subject of numerous simulation studies [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. * dietmar.paschek@udo.edu; http://ganter.chemie.uni-dortmund.de/~pas/ Hydrophobic effects are considered to play an important role concerning protein stability and other self assembly phenomena [4,28,29].…”

Low-temperature and high-pressure induced swelling of a hydrophobic polymer-chain in aqueous solution

“…In particular, they are seen as an important driving force with regard to the folding of proteins [4,5,6]. Consequently, a wealth of studies of hydrophobic interactions using molecular simulation techniques have been undertaken over the past three decades [7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]. Simulation studies have revealed that the contact state of a pair of hydrophobic particles in aqueous solution is entropically stabilized at ambient conditions [10,11].…”