UNDERSTANDING PROTEIN FOLDING AND STABILITY: A COMPUTATIONAL AND EXPERIMENTAL AP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议使用小角X射线散射来研究未折叠蛋白质的特征，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。尽管许多研究人员使用SAXS和其他技术来研究未折叠蛋白质，但对结果的解释通常仅限于将散射数据与高度理想化的模型的预测进行比较，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。为了解决这一困难，我们设计了一系列实验，使我们能够直接将观测到的散射分布与我们根据真实氨基酸序列通过计算生成的显式构象系综预测的散射分布进行比较。

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.