The Midwest Center for Structural Genomics

描述（由申请人提供）：本提案是由阿贡国家实验室、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、华盛顿大学联合提出的建立中西部结构基因组学中心（MCSG）的联合申请; MCSG是蛋白质结构倡议的大规模中心。MCSG的主要目的是快速确定战略选择的生物医学重要和高价值的目标，包括来自病原体和高等真核生物的蛋白质的结构。我们的目标是阐明蛋白质折叠空间，并最终提供足够的粒度，允许所有蛋白质的3D同源性建模，只使用计算方法的主要蛋白质家族的结构覆盖。这将为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将在蛋白质数据库（PDB）中找到或通过计算方法推导出来。 MCSG将通过在第三代同步加速器上实施和改进快速、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使命至关重要的先进数据管理系统和数据库。在PSI试验阶段，MCSG建立了一个结构确定平台，包括：（1）对所有可用的基因组序列进行分类以建立优先化的靶组，（2）克隆和表达微生物和真核生物来源的基因和基因片段，（3）纯化和结晶天然和衍生的蛋白质用于X射线晶体学，（4）收集数据和确定结构，（5）分析结构以进行折叠和功能分配，以及相关蛋白质的同源建模。该平台提供了快速的模型验证和PDB沉积。在PSI-2中，这些步骤将进一步推进，并使用LIMS和数据库集成到一个每年能够确定200多个结构的系统中。 MCSG组织是一个非常有效和成功的联盟，反映了结构基因组学生产中心的规模和复杂性的一个很好的例子。我们的多机构联盟已经组建了一个高度整合的跨学科团队，准备进入PSI-2的生产阶段。我们建议与科学界积极互动，为PSI网络知识库做出贡献，进行技术培训，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。

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.