COMPUTER STUDIES OF PRESSURE EFFECTS AND PROTEIN HYDRATI

溶解溶质光谱随压力变化的研究 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，压力已被单独用作环境因素。 变量来探索蛋白质与配体的相互作用，以研究 构象平衡和蛋白质动力学。压力依赖 蛋白质展开的研究也是一个广泛研究的课题。非常 最近，高分辨率X射线和核磁共振技术已被用于 获取有关压力效应的原子分辨率信息 蛋白质。拟议研究的总体目标是进一步 通过计算机模拟探索外加压力对 蛋白质构象的平衡和动态方面，特别是 探索蛋白质-溶剂界面的性质。在预赛中 一种引人注目的胰腺胰蛋白酶抑制剂的压力效应研究 观察到蛋白质水化层有很大的可压缩性。一个 将制定框架，以便更系统地描述 蛋白质水合层的热力学性质。的研究 对胰腺胰蛋白酶抑制剂的压力效应将扩大到 高分辨率数据中的溶菌酶和葡萄球菌核酸酶 可用于与模拟进行比较。较小规模的模拟 还将实施示范系统，以帮助澄清这一关系 蛋白质水合层的热力学性质和 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.