Structural Genomics of Eukaryotic Domain Families

真核域家族的结构基因组学

• 批准号: 7090571
• 负责人: GAETANO T MONTELIONE
• 金额: $ 1015.85万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090571
• 关键词: X ray crystallography; biomedical resource; cooperative study; functional /structural genomics; molecular biology information system; nuclear magnetic resonance spectroscopy; protein structure; proteomics

DESCRIPTION (provided by applicant): The Northeast Structural Genomics Consortium (NESG) , established in 2000, has pioneered high throughput (HTP) protein structure determination, demonstrating that HTP protein production is feasible and benefits tremendously from economies of scale. The long term goal of the NESG is to determine representative three-dimensional structures of the repertoire of protein domain families that constitute higher eukaryotic proteomes, with particular emphasis on the human proteome. In order to achieve this goal, the NESG will continue to develop a scalable and efficient platform for HTP protein sample and structure production. NESG proposes an expansion of its current platform, which will allow protein structure production by X-ray crystallography and nuclear magnetic resonance spectroscopy at rates of 150 - 200 protein structures per year, providing some 850 - 900 non-redundant protein structures over a 5 yr period. Technology development will focus on production and structure analysis of eukaryotic proteins using robotic methods. The NESG protein targets are selected from large protein domain sequence families so as to provide representative structures from these families, and to improve our understanding of protein sequence-structure space. Targets will also be prioritized based on functional relationships, using biological network analyses of co-functioning proteins involved in human cancers and developmental diseases. The high scientific value of our structure analysis efforts will be ensured by cutting edge bioinformatics activities, including target selection, protein interaction network analysis, computational structure/function annotation, homology modeling, and advanced data management and mining activities. The many methods and technologies for structural genomics research developed in this project will provide the next-generation tools for traditional hypothesis-driven structural biology research, and will thus have powerful and broad impact on the infrastructure for scientific research in the United States.

描述（由申请人提供）：东北结构基因组学联盟 (NESG) 成立于 2000 年，开创了高通量 (HTP) 蛋白质结构测定的先河，证明 HTP 蛋白质生产是可行的，并且可以从规模经济中获益匪浅。 NESG 的长期目标是确定构成高等真核蛋白质组的蛋白质结构域家族的代表性三维结构，特别强调人类蛋白质组。为了实现这一目标，NESG 将继续开发可扩展且高效的 HTP 蛋白质样品和结构生产平台。 NESG 提议扩展其当前平台，通过 X 射线晶体学和核磁共振波谱法以每年 150 - 200 个蛋白质结构的速度生产蛋白质结构，在 5 年内提供约 850 - 900 个非冗余蛋白质结构时期。技术开发将集中于使用机器人方法生产和分析真核蛋白质。 NESG蛋白靶标选自大蛋白结构域序列家族，以提供这些家族的代表性结构，并提高我们对蛋白质序列结构空间的理解。还将利用与人类癌症和发育疾病相关的协同功能蛋白的生物网络分析，根据功能关系对目标进行优先排序。我们的结构分析工作的高科学价值将通过尖端的生物信息学活动来确保，包括目标选择、蛋白质相互作用网络分析、计算结构/功能注释、同源建模以及先进的数据管理和挖掘活动。该项目开发的多种结构基因组学研究方法和技术将为传统假设驱动的结构生物学研究提供下一代工具，从而对美国的科学研究基础设施产生强大而广泛的影响。