MODELING PROTEIN STRUCTURE USING SPARSE NMR CONSTRAINTS

使用稀疏 NMR 约束对蛋白质结构进行建模

• 批准号: 8361793
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361793
• 关键词: Cell surface; Coupling; Data; Funding; Goals; Grant; Homology Modeling; Methods; Modeling; National Center for Research Resources; Oligosaccharides; Principal Investigator; Proteins; Research; Research Infrastructure; Residual state; Resources; Source; Structure; United States National Institutes of Health; Universities; Washington; Work; cost; design; glycosyltransferase; improved; programs; protein structure; restraint

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 获得许多在细胞表面寡糖（例如糖基转移酶）合成中重要的蛋白质的实验结构信息一直很困难。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烈打击，一些结构可以进行同源建模，而其他结构可以通过精心设计的力场进行预测。该项目的目标是探索使用残余偶极耦合（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。研究资源将向华盛顿大学贝克小组等计算小组提供模型蛋白质以及糖基转移酶的 RDC 和距离数据，以便他们可以修改其方法以适应这些类型的 NMR 数据的包含。我们的目标是开发结构测定方法，该方法可以处理具有挑战性的蛋白质，但只能获得有限数量的结构数据。