Molecular dynamics simulations of pressure effects on hydrophobic interactions
Molecular dynamics simulations of pressure effects on hydrophobic interactions
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DOI：
10.1021/ja010446v
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发表时间：
2001-11-07
影响因子：
15
通讯作者：
Garde, S
中科院分区：
文献类型：
--
作者：
Ghosh, T;García, AE;Garde, S
我们报告了从水中甲烷水溶液的分子动力学模拟中获得的压力对疏水相互作用的影响结果。研究了与蛋白质压力变性相关的各种压力。发现疏水性溶质之间水介导的相互作用的特征是压力依赖性的。特别是，随着压力的增加，我们发现（1）平均力（PMF）的溶质-溶质势中的溶剂分离构型相对于接触构型是稳定的； (2) 去溶剂化势垒相对于接触构型和溶剂分离构型均单调增加； (3) 极小值和障碍的位置向更短的间隔移动； (4) 对于较大的疏水性溶质，压力效应会显着放大。总之，这些观察结果为 Hummer 等人先前提出的压力变性过程的观点提供了强有力的支持。 (Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1552)：随着压力的增加，水转移到蛋白质内部成为压力变性过程的关键，导致紧密疏水接触的解离以及随后通过水分子的插入使疏水性蛋白质内部膨胀。较大疏水性溶质之间 PMF 的压力依赖性表明，与甲烷-甲烷 PMF 相比，压力对疏水性氨基酸之间相互作用的影响可能会大大放大。
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.