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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 蛋白质结构测定的实验库非常发达，并且是在世界各地各种蛋白质晶体学光束线上进行的典型研究。尽管水环境是蛋白质三级结构的重要决定因素，但目前可用于表征水环境结构和力的实验工具相对较少。我们结合了我们在广角溶液散射实验，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合结构和力。本建议的目的是将我们对这些简化模型系统的广角实验扩展到小角度X射线散射，以研究疏水效应和水合水的作用。这些新的实验，需要一个高通量光谱仪，覆盖Q < 0.4 A-1，将使我们能够解决一个重要的生物物理问题，水化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.