MODELING PROTEIN STRUCTURE USING SPARSE NMR CONSTRAINTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 对于许多在细胞表面寡糖合成中起重要作用的蛋白质（例如糖基转移酶），很难获得实验结构信息。然而，这些蛋白质中的许多显示出来自计算线程程序的强烈命中，一些结构可以被同源建模，而其他结构可以从精心设计的力场中预测。本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，以提高搜索效率和结构的质量。研究资源将提供RDC和模型蛋白质的距离数据，以及糖基转移酶，计算组，如贝克组在华盛顿大学，使他们能够修改他们的方法，以适应这些类型的NMR数据的列入。其目标是开发用于结构测定的方法，该方法可以用于仅可以获得有限数量的结构数据的具有挑战性的蛋白质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.