The Midwest Center for Structural Genomics

该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、 华盛顿大学建立中西部结构基因组学中心（MCSG）; 蛋白质结构倡议。MCSG的主要目标是快速确定战略性的 选定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 目的是阐明蛋白质折叠空间，并最终提供主要蛋白质家族的结构覆盖， 足够的粒度允许仅使用计算方法对所有蛋白质进行3D同源建模。这将提供 21世纪世纪结构生物学的基础，届时几乎所有蛋白质的结构都将在蛋白质数据中找到 银行（PDB）或通过计算方法得出。 MCSG将通过实施和改进快速、高度集成和具有成本效益的方法来实现这些目标， 在第三代同步加速器上通过X射线晶体学进行结构测定。我们将继续发展 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）将所有可用的基因组序列分类， 建立优先目标集，（2）克隆和表达微生物和真核生物的基因和基因片段 来源，（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， 确定结构，（5）分析折叠和功能分配的结构，以及相关的同源性建模。 proteins.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 使用LIM和数据库先进并集成到一个系统中，该系统每年能够确定200多个结构， 每个结构的成本<5万美元。 MCSG组织是一个非常有效和成功的联盟的典范，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个 高度整合和跨学科的团队准备进入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， 将使所有的方法和结果在这个程序的过程中开发随时提供给科学界。

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 at a cost of <$50K per structure. 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.