COMPUTER STUDIES OF PRESSURE EFFECTS AND PROTEIN HYDRATI

溶解溶质光谱的压力依赖性研究 提供了大量关于溶质-溶剂相互作用的信息。 在生物物理化学中，压力一直被用作环境因素。 变量来探测蛋白质与配体的相互作用， 构象平衡和蛋白质动力学。 压力依赖性 蛋白质解折叠也是一个广泛研究的课题。 非常 最近，高分辨率X射线和NMR技术已被用于 获得关于压力对 proteins. 拟议研究的总体目标是进一步 通过计算机模拟探索施加压力对 蛋白质构象的平衡和动态方面，特别是 来探测蛋白质-溶剂界面的性质。 在初步 胰蛋白酶抑制剂的压力效应的研究， 观察到蛋白质水合层的大的可压缩性。 一 将制定一个框架，以更系统地描述 蛋白质水化层的热力学性质。 研究 压力对胰蛋白酶抑制剂的影响将扩大到 溶菌酶和葡萄球菌核酸酶，其中高分辨率数据 可与模拟进行比较。 模拟较小 还将建立模型系统，以帮助澄清这种关系 蛋白质水化层的热力学性质和 潜在的溶质-溶剂相互作用。

Pressure-dependent studies of the optical spectra of dissolved solutes have provided a wealth of information about solute-solvent interactions. In biophysical chemistry, pressure has lone been used as an environmental variable to probe the interactions of proteins with ligands, to study conformational equilibria and protein dynamics. The pressure dependence of protein unfolding has also been a subject of extensive study. Very recently, high resolution X-ray and NMR techniques have been used to obtain atomic resolution information concerning pressure effects on proteins. The overall objective of the proposed research is to further explore through computer simulations the effects of applied pressure on equilibrium and dynamic aspects of protein conformation, and in particular to probe the nature of the protein-solvent interface. In a preliminary study of pressure effects on Pancreatic Trypsin Inhibitor, a strikingly large compressibility of the protein hydration layer was observed. A framework will be developed to characterize more systematically the thermodynamic properties of the protein hydration layer. Studies of pressure effects on Pancreatic Trypsin Inhibitor will be extended to lysozyme and staphylococcal nuclease where high resolution data is available to comparison with the simulations. Simulations of smaller model systems will also be carried out to help clarify the relationship between the thermodynamic properties of the protein hydration layer and the underlying solute-solvent interactions.