SMALL ANGLE X-RAY SCATTERING AND HYDRATION FORCES IN PROTEIN FOLDING

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。蛋白质结构测定的实验体系非常发达，是在世界各地各种蛋白质结晶学光束线上进行的典型研究。尽管人们认识到水环境是蛋白质三级结构的重要决定因素，但目前从结构和作用力方面表征水环境的实验工具相对较少。我们结合了我们在广角溶液分散实验、模拟和理论方面的专业知识，定义了一种模型系统方法，以确定蛋白质折叠早期和后期的水化结构和力。这个方案的目的是将我们在这些简化模型系统上的广角实验推广到小角x射线散射，研究疏水效应和水合水的作用。这些新的实验需要一台覆盖Q&lt；0.4A-1的高通量光谱仪，这将使我们能够解决一个重要的生物物理问题，即水合力在蛋白质折叠中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The experimental repertoire of protein structure determination is highly developed, and is typical of research conducted at the various protein crystallography beam lines around the world. Even though it is well appreciated that water environment is a vital determinant of protein tertiary structure, the experimental tools available to characterize aqueous environment in terms of structure and forces are comparatively minimal at present. We have combined our expertise in wide-angle solution scattering experiments, simulations, and theory, to define a model systems approach to determine hydration structure and forces in both early and late stages of protein folding. The aim of this proposal is to extend our wide-angle experiments on these simplified model systems to small angle x-ray scattering, to study the role of the hydrophobic effect and the hydration water. These new experiments, requiring an high flux spectrometer that cover Q < 0.4 A-1, will allow us to address an important biophysical question as to the role of hydration forces in protein folding