DE NOVO PROTEIN STRUCTURE GENERATION FROM INCOMPLETE CHEMICAL SHIFT ASSIGNMENTS

不完整的化学位移分配从头生成蛋白质结构

• 批准号: 7957681
• 负责人: Ad - Bax
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957681
• 关键词: Biology; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Data; Funding; Fungal Genome; Generations; Grant; Institution; Methods; Process; Proteins; Protocols documentation; Research; Research Personnel; Resources; Simulate; Source; Structure; United States National Institutes of Health; improved; protein structure; solid state nuclear magnetic resonance

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. NMR chemical shifts provide important local structural information for proteins. Consistent structure generation from NMR chemical shift data has recently become feasible for proteins with sizes of up to 130 residues, and such structures are of a quality comparable to those obtained with the standard NMR protocol. This study investigates the influence of the completeness of chemical shift assignments on structures generated from chemical shifts. The Chemical-Shift-Rosetta (CS-Rosetta) protocol was used for de novo protein structure generation with various degrees of completeness of the chemical shift assignment, simulated by omission of entries in the experimental chemical shift data previously used for the initial demonstration of the CS-Rosetta approach. In addition, a new CS-Rosetta protocol is described that improves robustness of the method for proteins with missing or erroneous NMR chemical shift input data. This strategy, which uses traditional Rosetta for pre-filtering of the fragment selection process, is demonstrated for two paramagnetic proteins and also for two proteins with solid-state NMR chemical shift assignments.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 NMR化学转移为蛋白质提供了重要的局部结构信息。 NMR化学移位数据的一致结构生成最近对于具有多达130个残基的蛋白质而言是可行的，并且这种结构具有与标准NMR协议获得的质量相当的质量。这项研究研究了化学转移分配完整性对化学位移产生的结构的影响。化学转移 - 罗塞塔（CS-Rosetta）方案用于从头蛋白结构的产生，具有不同程度的化学位移分配，这是通过省略条目在先前用于CS-Rosetta方法初始证明的实验化学移位数据中模拟的。此外，描述了一种新的CS-Rosetta方案，该方案可改善具有缺失或错误的NMR化学位移输入数据的蛋白质方法的鲁棒性。该策略使用传统的罗塞塔（Rosetta）进行片段选择过程进行过滤，并为两种顺磁性蛋白以及两个具有固态NMR化学移位分配的蛋白质提供了证明。