FOLDING DYNAMICS OF COMPUTATIONALLY DESIGNED PROTEINS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一个旨在了解蛋白质如何使用实验和计算技术折叠的项目。后者可以指导快速文件夹和结构一致的突变体的搜索。我们将采用的计算技术使用统计热力学来识别蛋白质序列中的挫折位置以及结构一致和较少挫折的突变。此方法以前曾用于指导快速文件夹的搜索。在这种情况下，它已被应用于20个残基的微蛋白，色氨酸笼，在努力减少其4微秒的折叠时间进一步。我们将使用的实验技术包括激光诱导温度跳跃动力学实验（红外或紫外检测）以及静态实验，使用荧光，红外光谱和圆二色性。

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. This is a project aimed to understand how proteins fold using both experimental and computational techniques. The latter can guide the search for fast folders and also structurally consistent mutants. The computational technique we will employ uses statiscal thermodynamics to identify frustrated positions in the protein sequence as well as structurally consistent and less frustrating mutations. This method has been used previously to guide the search for fast folders. In this case, it has been applied to the 20 residue miniprotein, Trp-cage, in an effort to decrease its 4 microsecond folding time further. The experimental techniques we will use include laser induced temperature-jump kinetics experiments (with IR or UV detection) as well as static experiments using fluorescence, infrared spectroscopy, and circular dichroism.