Midwest Center for Structural Genomics

描述（由申请人提供）：中西部结构基因组学中心（MCSG）的主要目标将是应用其结构确定管道来协作确定PSI：生物学网络和更广泛的生物学社区提名的靶标的结构。MCSG将与PSl的同事们一起，投入更小的精力，通过靶向那些结构可以提供序列和结构之间关系的蛋白质，来更广泛地覆盖蛋白质折叠空间。最后，MCSG将继续推动三个科学项目：人类病原体中与毒力相关的蛋白质，人类微生物组中与疾病相关的蛋白质，以及参与信号和转录调节的蛋白质——我们已经在与科学界的领导者合作追求这一领域。作为其任务的一部分，MCSG还将继续开发和改进技术，并改进快速、高度集成和经济有效的方法，通过使用第三代同步加速器X射线源的高性能光束线，通过X射线晶体学重新确定结构。我们的最终目标是与我们的PSl同事一起建立一个21世纪结构生物学的基础，在这个基础上，几乎任何蛋白质或蛋白质复合物的结构都将通过蛋白质数据库提供给生物界。MCSG将通过在第三代同步加速器上实施和改进快速、高度集成和具有成本效益的x射线晶体学结构测定方法来实现这些目标。我们将继续发展对主要任务至关重要的先进数据管理系统和数据库。MCSG建立了一个结构测定平台，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)克隆和表达微生物和真核起源的基因和基因片段；(3)纯化和结晶原生和衍生蛋白用于x射线晶体学；(4)收集数据和确定结构；(5)分析结构进行折叠和功能分配，以及相关蛋白的同源性建模。该平台提供了快速的模型验证和沉积在PDB。在PSI：生物学中，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。

DESCRIPTION (provided by applicant): The primary objective of the Midwest Center for Structural Genomics (MCSG) will be to apply its structure determination pipeline to collaboratively determine the structures of targets nominated by the PSI:Biology Network and the broader biology community. The MCSG will devote a smaller fraction of its effort to contribute, together with its PSl colleagues, to a broader coverage of protein fold space by targeting proteins whose structures would provide the greatest insight into the relationships between sequence and structure. Finally, the MCSG will continue to drive three scientific programs: proteins associated with virulence in human pathogens, proteins overrepresented and associated with disease in human microbiomes and proteins involved in signaling and transcription regulation - an area we are already pursuing in collaboration with leaders in the scientific community. As part of its mandate, the MCSG will also continue to develop and improve technology, and to refine rapid, highly integrated, and cost-effective methods for de novo structure determination by X-ray crystallography using high-performance beamlines at third-generation synchrotron X- ray sources. Our ultimate goal is to build, together with our PSl colleagues, a foundation for 21st century structural biology where the structures of virtually any protein or protein complex will be available to the biology community through the Protein Data Bank. 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. The MCSG established a structure determination platform that include: (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:Biology, these steps will be further advanced and integrated using LIMs and databases into a system capable of determining 200+ structures per year.