Midwest Center for Structural Genomics

中西部结构基因组学中心

• 批准号: 8246555
• 负责人: ANDRZEJ JOACHIMIAK
• 金额: $ 55.64万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246555
• 关键词: Advanced Development; Area; Bioinformatics; Biology; Cloning; Collaborations; Collection; Communities; Crystallization; Data; Databases; Deposition; Development; Disease; Foundations; Generations; Genes; Genome; Genomics; Goals; Homology Modeling; Human; Human Microbiome; Informatics; Methods; Mission; Modeling; Peer Review; Performance; Production; Protein Family; Protein Structure Initiative; Proteins; Publications; Research; Roentgen Rays; Scientist; Signal Transduction; Solutions; Source; Structural Models; Structure; Synchrotrons; System; Technology; Time; Transcriptional Regulation; Validation; Virulence; Visit; X-Ray Crystallography; base; beamline; cost effective; data management; high throughput technology; improved; insight; interest; knowledge base; microbial; pathogen; programs; protein complex; protein expression; protein folding; repository; research facility; structural biology; structural genomics; synchrotron radiation; tool

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.

中西部结构基因组学中心 (MCSG) 的主要目标是应用其结构 确定管道，以协作确定 PShBlology 提名的目标结构 网络和更广泛的生物学界。 MCSG 将投入一小部分精力 与其 PSl 同事一起，通过靶向蛋白质来扩大蛋白质折叠空间的覆盖范围 其结构将提供对序列和结构之间关系的最深入的了解。 最后，MCSG 将继续推动三个科学项目：与毒力相关的蛋白质 人类病原体、蛋白质在人类微生物组中比例过高并与疾病相关， 参与信号传导和转录调控的蛋白质——我们已经在合作的领域 与科学界的领导者。作为其职责的一部分，MCSG 还将继续开发和 改进技术，并完善快速、高度集成且经济高效的从头结构方法 使用第三代同步加速器 X 射线的高性能光束线进行 X 射线晶体学测定 来源。我们的最终目标是与我们的 PSl 同事一起为 21 世纪奠定基础 结构生物学，几乎任何蛋白质或蛋白质复合物的结构都可供人们使用 生物学界通过蛋白质数据库。 MCSG 将通过实施和完善快速、高度集成且具有成本效益的方式来实现这些目标 在 3^"^ 代同步加速器上通过 X 射线晶体学确定结构的方法。我们将继续 开发对主要任务至关重要的先进数据管理系统和数据库。 MCSG建立了一个结构确定平台，包括：（1）对所有可用的基因组进行分类 序列以建立优先目标集，（2）克隆和表达基因和基因片段 微生物和真核起源，(3) 纯化和结晶天然和衍生蛋白用于 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 并沉积在 PDB 中。在 PShBiology 中，这些步骤将使用 LIM 和 将数据库集成到每年能够确定 200 多个结构的系统中。