Smolin Nikolai, Winter Roland
Physical Chemistry and Biophysical Chemistry, Department of Chemistry, University of Dortmund, Otto-Hahn-Str. 6, D-44227 Dortmund, Germany.
J Phys Chem B. 2008 Jan 24;112(3):997-1006. doi: 10.1021/jp076440v. Epub 2008 Jan 3.
It is now generally agreed that the hydration water and solvational properties play a crucial role in determining the dynamics and hence the functionality of proteins. We present molecular dynamics computer simulation studies on staphylococcal nuclease (SNase) at various temperatures and pressures as well as in different cosolvent solutions containing various concentrations of urea and glycerol. The aim is to provide a molecular level understanding of how different types of cosolvents (chaotropic and kosmotropic) as well as temperature and high hydrostatic pressure modify the structure and dynamics of the hydration water. Taken together, these three intrinsic thermodynamic variables, temperature, pressure, and chemical potential (or activity) of the solvent, are able to influence the stability and function of the protein by protein-solvent dynamic coupling in different ways. A detailed analysis of the structural and dynamical properties of the water and cosolvents at the protein surface (density profile, coordination numbers, hydrogen-bond distribution, average H-bond lifetimes (water-protein and water-water), and average residence time of water in the hydration shell) was carried out, and differences in the structural and dynamical properties of the hydration water in the presence of the different cosolvents and at temperatures between 300 and 400 K and pressures up to 5000 bar are discussed. Furthermore, the results obtained help understand various thermodynamic properties measured for the protein.
现在人们普遍认为，水合水和溶剂化性质在决定蛋白质的动力学以及功能方面起着至关重要的作用。我们进行了分子动力学计算机模拟研究，考察了葡萄球菌核酸酶（SNase）在不同温度、压力下以及在含有不同浓度尿素和甘油的不同共溶剂溶液中的情况。目的是从分子层面理解不同类型的共溶剂（促溶剂和助溶剂）以及温度和高静水压如何改变水合水的结构和动力学。总之，溶剂的这三个内在热力学变量，即温度、压力和化学势（或活度），能够通过蛋白质 - 溶剂动态耦合以不同方式影响蛋白质的稳定性和功能。我们对蛋白质表面水和共溶剂的结构与动力学性质进行了详细分析（密度分布、配位数、氢键分布、平均氢键寿命（水 - 蛋白质和水 - 水）以及水在水合壳层中的平均停留时间），并讨论了在不同共溶剂存在下以及温度在300至400 K、压力高达5000巴时水合水结构和动力学性质的差异。此外，所获得的结果有助于理解针对该蛋白质测量的各种热力学性质。
