The Midwest Center for Structural Genomics

这项提议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、 华盛顿大学将建立中西部结构基因组学中心(MCSG)；一个大规模的 蛋白质结构倡议。MCSG的主要目标是迅速确定战略上的 选定的生物医学重要和高价值目标，包括来自病原体和高等真核生物的蛋白质。这个 目标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世纪结构生物学的基础，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 第三代同步加速器X射线结晶学结构测定。我们将继续发展 对主要特派团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，该平台包括：(1)对所有可用的基因组序列进行分类 建立优先目标集，(2)微生物和真核生物基因和基因片段的克隆和表达 来源，(3)纯化和结晶天然和衍生的蛋白质用于X射线结晶学，(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，以及相关的同源建模 蛋白质。该平台提供了快速模型验证和在PDB中的沉积。在PSI-2中，这些步骤将进一步 使用LIM和数据库高级集成到一个每年能够确定200多个结构的系统中 每个结构的成本&lt；$50K。 MCSG组织是一个高效和成功的财团的典范，反映了 结构基因组学生产中心的规模和复杂性。我们的多机构财团已经组建了一个 高度一体化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，为防扩散安全倡议网络知识库作出贡献，开展技术培训和 将使在该计划过程中开发的所有方法和结果随时可供科学界使用。

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.