Midwest Center for Structural Genomics

中西部结构基因组学中心

• 批准号: 8300848
• 负责人: ANDRZEJ JOACHIMIAK
• 金额: $ 688.4万
• 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/8300848
• 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; Internet; 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; metagenome; microbial; pathogen; programs; protein complex; protein expression; protein folding; repository; research facility; structural biology; structural genomics; synchrotron radiation; tool

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.

描述（由申请人提供）：中西部结构基因组学中心（MCSG）的主要目标是应用其结构测定管道来协作确定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将投入一小部分努力，与其PS1同事一起，通过靶向其结构将提供对序列和结构之间关系的最大洞察的蛋白质，来贡献更广泛的蛋白质折叠空间覆盖。最后，MCSG将继续推动三个科学计划：与人类病原体毒力相关的蛋白质，与人类微生物组中疾病相关的蛋白质，以及参与信号传导和转录调控的蛋白质-我们已经与科学界的领导者合作开展的领域。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，高度集成和具有成本效益的方法，用于在第三代同步加速器X射线源上使用高性能光束线通过X射线晶体学进行从头结构测定。我们的最终目标是与我们的PSl同事一起为21世纪的结构生物学奠定基础，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建立了一个结构确定平台，包括：（1）对所有可用的基因组序列进行分类以建立优先化的靶组，（2）克隆和表达微生物和真核生物来源的基因和基因片段，（3）纯化和结晶天然和衍生的蛋白质用于X射线晶体学，（4）收集数据和确定结构，（5）分析结构以进行折叠和功能分配，以及相关蛋白质的同源建模。该平台提供了快速的模型验证和PDB沉积。在PSI：生物学中，这些步骤将进一步推进，并使用LIM和数据库集成到一个每年能够确定200多个结构的系统中。