Dias Cristiano L, Chan Hue Sun
Department of Physics, New Jersey Institute of Technology, University Heights , Tiernan Hall, Room 463, Newark, New Jersey 07102, United States.
Departments of Biochemistry, Molecular Genetics, and Physics, University of Toronto , 1 King's College Circle, Toronto, Ontario Canada M5S 1A8.
J Phys Chem B. 2014 Jul 10;118(27):7488-7509. doi: 10.1021/jp501935f. Epub 2014 Jun 30.
Hydration effects on a pair of methane molecules are investigated by extensive constant-pressure (NPT) sampling using the TIP4P model of water under 1, 1000, 2000, and 3000 atm. The volume distributions of pure water and of methanes plus water are determined directly as functions of methane-methane distance ξ. The corresponding excess isothermal and adiabatic compressibilities are estimated from the pressure-dependent methane excess volume. The dependence of excess volume on ξ is oscillatory for small ξ. The maxima of excess volume and compressibility are seen near the desolvation barrier (db) of the potential of mean force (PMF). These features may be understood by the development, near the db, of a void volume encased by a molecular (Connolly) surface defined using a water-sized probe. These db properties for two methanes are consistent with well-corroborated experimental observations of positive activation volumes for protein folding and some experiments suggesting a slightly higher compressibility for the folding transition state than the unfolded state. At high pressures, the volumes at the PMF solvent-separated minimum and the contact-minimum configurations are both smaller than the volume at large ξ. This trend provides a rationalization for the compactness of pressure-denatured states of proteins. Taking the packing densities of pure nonpolar phases into consideration, our simulation results suggest that whether the activation volume of unfolding is positive or negative hinges on the packing compactness of the protein core. Volume change can be but is not necessarily monotonic along the folding pathway.
利用TIP4P水模型，在1、1000、2000和3000个大气压下，通过广泛的恒压（NPT）采样研究了水合作用对一对甲烷分子的影响。纯水以及甲烷与水混合物的体积分布直接作为甲烷 - 甲烷距离ξ的函数来确定。根据与压力相关的甲烷过量体积估算相应的过量等温压缩率和绝热压缩率。对于较小的ξ，过量体积对ξ的依赖性呈振荡性。在平均力势（PMF）的去溶剂化屏障（db）附近可以看到过量体积和压缩率的最大值。这些特征可以通过在db附近形成一个由使用水尺寸探针定义的分子（康诺利）表面所包围的空体积来理解。两个甲烷的这些db性质与蛋白质折叠的正活化体积的充分证实的实验观察结果以及一些实验一致，这些实验表明折叠过渡态的压缩率略高于未折叠态。在高压下，PMF溶剂分离最小值和接触最小值构型处的体积均小于大ξ处的体积。这种趋势为蛋白质压力变性状态的紧凑性提供了一种解释。考虑到纯非极性相的堆积密度，我们的模拟结果表明，展开的活化体积是正还是负取决于蛋白质核心的堆积紧凑性。沿着折叠途径，体积变化可能是但不一定是单调的。
