UNDERSTANDING PROTEIN FOLDING AND STABILITY: A COMPUTATIONAL AND EXPERIMENTAL AP

这个子项目是许多研究子项目中的一个 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， 因此可以在其他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。 我们建议使用小角度X射线散射来研究未折叠蛋白质的特性，这是一个长期存在的问题，对于理解蛋白质折叠的机制和决定蛋白质稳定性的因素具有重要意义。虽然许多研究人员已经使用SAXS和其他技术来研究未折叠的蛋白质，结果的解释通常仅限于散射数据与高度理想化模型的预测的比较，这些模型没有明确考虑排除的体积效应或与溶剂的相互作用。由于这个原因，以及其他原因，关于未折叠蛋白质的性质仍然存在很大的不确定性和争议。为了解决这个困难，我们设计了一组实验，使我们能够直接比较观察到的散射曲线与我们预测的计算生成的合奏明确的构象的基础上真实的氨基酸序列。

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. We propose to use small-angle x-ray scattering to study the character of unfolded proteins, a long standing problem with important implications for understanding the mechanisms of protein folding and the factors that determine protein stability. Although numerous investigators have used SAXS and other techniques to study unfolded proteins, the interpretation of the results has usually been limited to comparisons of scattering data with predictions from highly idealized models that do not account explicitly for excluded volume effects or interactions with the solvent. For this reason, as well as others, there remains a great deal of uncertainty and controversy about the nature of unfolded proteins. To address this difficulty, we have designed a set of experiments that with enable us to directly compare the observed scattering profiles with those we predict from computationally-generated ensembles of explicit conformations based on real amino acid sequences.