The Midwest Center for Structural Genomics

中西部结构基因组学中心

• 批准号: 6961322
• 负责人: ANDRZEJ JOACHIMIAK
• 金额: $ 920万
• 依托单位: UNIVERSITY OF CHICAGO
• 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/6961322
• 关键词: X ray crystallography; biomedical resource; cooperative study; functional /structural genomics; molecular biology information system; protein structure; proteomics

DESCRIPTION (provided by applicant): This proposal is a joint application from the Argonne National Laboratory, European Bioinformatics Institute, Northwestern University, University College London, University of Texas, University of Toronto, University of Virginia, Washington University to establish the Midwest Center for Structural Genomics (MCSG); a Large-Scale Center of the Protein Structure Initiative. The primary objective of the MCSG is to rapidly determine the structures of strategically selected bio-medically important and high-value targets including proteins from pathogens and higher eukaryotes. The goal is to elucidate protein folding space and ultimately provide structural coverage of major protein families with sufficient granularity to allow 3D homology modeling of all proteins using only computational methods. This will provide the foundation for 21st century structural biology when structures of virtually all proteins will be found in the Protein Data Bank (PDB) or derived by computational methods. MCSG will achieve these goals by implementing and refining rapid, highly integrated and cost effective methods for structure determination by x-ray crystallography at 3rd generation synchrotrons. We will continue development of advanced data management systems and databases that are vital to the primary mission. In the PSI pilot phase, the MCSG established a structure determination platform that included: (1) classifying all available genomic sequences to establish a prioritized target set, (2) cloning, and expressing genes and gene fragments of microbial and eukaryotic origin, (3) purifying and crystallizing native and derivatized protein for x-ray crystallography, (4) collecting data and determining structures, (5) analyzing structures for fold and function assignment, and homology modeling of related proteins. The platform provides for rapid model validation and deposition in PDB. In PSI-2, these steps will be further advanced and integrated using LIMS and databases into a system capable of determining 200+ structures per year. The MCSG organization is an excellent example of a highly effective and successful consortium that reflects the scale and complexity of a structural genomics production center. Our multi-institution consortium has assembled a highly integrated and interdisciplinary team prepared to enter the production phase of PSI-2. We propose to actively interact with the scientific community, contribute to the PSI Network Knowledge Base, conduct technology training and will make all methods and results developed in the course of this program readily available to the scientific community.

描述（申请人提供）：本提案是阿贡国家实验室、欧洲生物信息学研究所、西北大学、伦敦大学学院、德克萨斯大学、多伦多大学、弗吉尼亚大学、华盛顿大学联合申请建立中西部中心结构基因组学（MCSG）；蛋白质结构计划的大型中心。 MCSG 的主要目标是快速确定战略性选择的生物医学重要且高价值靶标的结构，包括来自病原体和高等真核生物的蛋白质。目标是阐明蛋白质折叠空间，并最终以足够的粒度提供主要蛋白质家族的结构覆盖，以便仅使用计算方法即可对所有蛋白质进行 3D 同源建模。这将为 21 世纪的结构生物学奠定基础，届时几乎所有蛋白质的结构都可以在蛋白质数据库 (PDB) 中找到或通过计算方法得出。 MCSG 将通过在第三代同步加速器上实施和完善快速、高度集成且具有成本效益的 X 射线晶体学结构测定方法来实现这些目标。我们将继续开发对主要任务至关重要的先进数据管理系统和数据库。在 PSI 试点阶段，MCSG 建立了一个结构确定平台，其中包括：(1) 对所有可用的基因组序列进行分类，以建立优先目标集，(2) 克隆和表达微生物和真核起源的基因和基因片段，(3 ) 纯化和结晶天然和衍生蛋白质，用于 X 射线晶体学，(4) 收集数据并确定结构，(5) 分析折叠和功能分配的结构，以及相关蛋白质的同源性建模。该平台提供 PDB 中的快速模型验证和存储。在 PSI-2 中，这些步骤将使用 LIMS 和数据库进一步推进并集成到每年能够确定 200 多个结构的系统中。 MCSG 组织是高效且成功的联盟的一个很好的例子，反映了结构基因组学生产中心的规模和复杂性。我们的多机构联盟已经组建了一支高度整合的跨学科团队，准备进入 PSI-2 的生产阶段。我们建议积极与科学界互动，为PSI网络知识库做出贡献，开展技术培训，并将在该计划过程中开发的所有方法和结果随时提供给科学界。