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、华盛顿大学联合申请建立中西部结构基因组学中心（MCSG）；大型蛋白质结构研究中心MCSG的主要目标是快速确定战略性选择的生物医学上重要和高价值靶标的结构，包括来自病原体和高级真核生物的蛋白质。目标是阐明蛋白质折叠空间，并最终提供具有足够粒度的主要蛋白质家族的结构覆盖，以便仅使用计算方法对所有蛋白质进行3D同源建模。这将为21世纪的结构生物学提供基础，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。

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.