MODELING PROTEIN STRUCTURE USING SPARSE NMR CONSTRAINTS

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。 在细胞表面低聚糖(例如糖基转移酶)的合成中，许多重要的蛋白质的实验结构信息都很难获得。然而，这些蛋白质中的许多都显示出来自计算线程程序的强大命中率，一些结构可以被同源建模，另一些可以从精心设计的力场中预测出来。该项目的目标是探索使用剩余偶极耦合(RDC)约束和顺磁距离约束来提高搜索效率和结果结构的质量。研究资源将向计算小组，如华盛顿大学的贝克小组，提供模型蛋白质以及糖基转移酶的RDC和距离数据，以便他们可以修改他们的方法，以适应这些类型的核磁共振数据的纳入。目标是开发结构确定方法，这种方法可以处理具有挑战性的蛋白质，而这些蛋白质只能获得有限数量的结构数据。

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. It has been difficult to obtain experimental structural information on many of the proteins important in the synthesis of cell-surface oligosaccharides (glycosyltransferases, for example). Yet, many of these proteins show strong hits from computational threading programs, some structures can be homology modeled, and others can be predicted from well designed force fields. The goal of this project is to explore the use of residual dipolar coupling (RDC) restraints and paramagnetic distance restraints in improving the efficiency of searches and the quality of the structures that result. The Research Resource will be providing RDC and distance data on model proteins, as well as glycosyltransferases, to the computational groups such as the Baker group at the University of Washington, so that they can modify their approaches to accommodate the inclusion of these types of NMR data. The goal is to develop methods for structure determination that can work with challenging proteins for which only limited amounts of structural data can be obtained.