Midwest Center for Structural Genomics

中西部结构基因组学中心（MCSG）的主要目标是将其结构 确定流水线，以协作地确定由PShBlology提名的目标的结构 网络和更广泛的生物学社区。MCSG将投入一小部分精力， 与其PSl同事一起，通过靶向蛋白质， 它的结构将提供对序列和结构之间关系的最大洞察力。 最后，MCSG将继续推动三个科学计划：与毒力相关的蛋白质， 人类病原体，在人类微生物组中与疾病相关的蛋白质， 参与信号传导和转录调节的蛋白质--我们已经在合作研究这一领域 与科学界的领导人进行交流作为其任务的一部分，MCSG还将继续发展和 改进技术，改进快速、高度集成和具有成本效益从头构造方法 使用第三代同步加速器X射线高性能光束线的X射线晶体学测定 源我们的最终目标是与我们的PSl同事一起为21世纪世纪奠定基础 结构生物学，其中几乎任何蛋白质或蛋白质复合物的结构将可用于 蛋白质数据库的数据。 MCSG将通过快速、高度集成和成本效益的实施和改进来实现这些目标 在第三代同步加速器上用X射线晶体学测定结构的方法。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。 MCSG建立了一个结构测定平台，包括：（1）对所有可用的基因组进行分类， 序列以建立优先化的靶集合，（2）克隆和表达以下基因和基因片段： 微生物和真核生物来源，（3）纯化和结晶天然和衍生的蛋白质用于X射线 晶体学，（4）收集数据并确定结构，（5）分析结构的折叠和功能 相关蛋白质的分配和同源性建模。该平台提供快速模型验证 和沉积在PDB中。在PShBiology中，这些步骤将进一步推进并使用LIM进行整合， 数据库整合到一个系统中，每年能够确定200多个结构。

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 PShBlology 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 Xray 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 3^"^ 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 PShBiology, these steps will be further advanced and integrated using LIMs and databases into a system capable of determining 200+ structures per year.