Core F: Structure

核心F：结构

• 批准号: 7980201
• 负责人: JOHN A GERLT
• 金额: $ 76.19万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-20 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7980201
• 关键词: Address; Binding; Characteristics; Communication; Computer Simulation; Core Protein; Crystallization; Data; Data Collection; Deposition; Docking; Evaluation; Evolution; Exhibits; Family; Fostering; Funding; Goals; Individual; Intervention; Ligands; Manuals; Modeling; New York; Positioning Attribute; Production; Protein Structure Initiative; Proteins; Recording of previous events; Research; Research Infrastructure; Resources; Staging; Structure; System; Triage; Work; base; design; design and construction; experience; flexibility; insight; meetings; member; protein distribution; protein purification; structural genomics

While the infrastructure and organization of the EFI are inspired by the PSI, there are significant differences in their objectives, which offer unique opportunities for the EFI. Historically, the primary focus of the PSI has been on increasing the structural coverage of fold and sequence space, and the structure of any member of a particular sequence family is a suitable representative of the entire family. Consequently, all PSI targets are subjected to extensive triage, and only those sequences exhibiting highly favorable characteristics at each step of the pipeline are taken fonward for structure determination. This approach maximizes fold/sequence coverage regardless of functional importance. In contrast, the EFI is explicitly concerned with the discovery of function and thus will frequently necessitate the study of recalcitrant sequences requiring efforts that exceed those commonly expended on any individual PSI target. Accordingly, the PC and SC are positioned to implement considerable primary and secondary rescue strategies in protein purification, crystallization, data collection and structure determination in order to successfully prosecute those targets that are most informative in terms of function, mechanism and evolution. In particular, as needed and detailed below, the expert technical staff of the SC is prepared to provide extensive and expanded efforts in crystallization, data collection and structure determination. Furthermore, beyond these traditional aspects of the structure discovery pipeline, the SC will devote considerable resources to ligand identification efforts in order to 1) obtain direct functional insights, 2) aid in crystallization, and 3) maximize the utility of structures for computational ligand discovery.

虽然EFI的基础设施和组织受到PSI的启发，但它们的目标存在重大差异，这为EFI提供了独特的机会。从历史上看，PSI的主要焦点一直是增加折叠和序列空间的结构覆盖率，而特定序列家族的任何成员的结构都是整个家族的合适代表。因此，所有PSI目标都是 经过广泛的分类，只有那些在管道的每一步表现出高度有利的特征的序列才被用于结构确定。这种方法使折叠/序列覆盖率最大化，而不考虑功能重要性。相比之下，EFI明确地关注功能的发现，因此经常需要研究顽固的序列，所需的努力超过 通常花费在任何单个PSI目标上。因此，PC和SC将在蛋白质纯化、结晶、数据收集和结构确定方面实施相当大的初级和次级救援策略，以便成功地起诉那些在功能、机制和进化方面最具信息量的靶标。特别是，根据需要并在下文中详细说明， SC准备在结晶、数据收集和结构确定方面提供广泛和扩大的努力。此外，除了结构发现流水线的这些传统方面之外，SC还将投入大量资源进行配体识别工作，以1)获得直接的功能见解，2)帮助结晶，以及3)最大限度地利用结构来进行计算配体发现。