Structural Genomics of Eukaryotic Domain Families

描述（由申请人提供）：东北结构基因组学联盟（NESG）是由NIH NIGMS蛋白质结构倡议（PSI）资助的四个大型结构生产中心（LSCs）之一。PSI LSCs的目标是：(i)为使用广泛的生物学、基因组学和生物信息学标准选择的大量蛋白质生成三维（3D）结构，以及从特定生物学主题项目中选择的靶标，从而提供大量蛋白质序列在自然界的重要结构覆盖，（ii）开发和传播结构生物学和生物信息学的新颖和/或改进技术，以及（iii）制造这些结构。构建生产数据，以及全球科学界公开可用的相关试剂和技术。在PSI计划的下一阶段PSI：生物学中，NESG将扩大其使命，与几个PSI高通量（HTP）结构生物学合作伙伴关系联盟（生物学合作伙伴关系）和相关的计划公告（par）一起开展我们的合作结构基因组学项目。NESG In PSI:Biology的主要目标是在5年内为蛋白质数据库（PDB）提供1000个新的3D蛋白质结构，以及广泛的原始和处理数据，样品生产协议，结构/功能注释以及从这些结构衍生的数千个同源模型。这将补充NESG在PSI第1和第2阶段沉积的约900个结构。特别是，NESG将为大量真核生物和人类蛋白质的建模提供新的3D结构信息。我们的工作将跨越五类靶标类型：(i)在与PSI生物学合作伙伴关系建立的合作中提名的蛋白质，（ii）由中央PSI定义的结构域家族（称为BIG， MEGA和META家族）：生物学靶标选择小组委员会提供大蛋白质结构域家族的细粒度覆盖；（iii）由NESG生物医学主题“与人类癌症和发育生物学相关的蛋白质网络”定义的蛋白质；（iv）一般生物医学研究界提名的蛋白质，(v)为特定技术开发目标选择的蛋白质。前两类的蛋白靶点约占NESG总体工作的80%，将与其他LSCs和生物学合作伙伴一起在协调过程中进行选择，以最大限度地提高生物学影响并减少冗余工作。本项目开发的许多结构基因组学研究方法和技术将为传统的假设驱动的生物学研究提供下一代工具，从而对生物科学和工程的基础设施产生强大而广泛的影响。

DESCRIPTION (provided by applicant): The Northeast Structural Genomics Consortium (NESG) is one of four Large-Scale Centers (LSCs) for structure production funded by the NIH NIGMS Protein Structure Initiative (PSI). The goals of the PSI LSCs are to (i) generate three-dimensional (3D) structures for large numbers of proteins selected using broad biological, genomic, and bioinformatics criteria, together with targets selected from specific biological theme projects, so as to provide significant structural coverage of a large number of protein sequences In nature, (ii) develop and disseminate novel and/or improved technologies for structural biology and bioinformatics, and (iii) make these structures, structure production data, and the associated reagents and technologies publicly available to the worldwide scientific community. In PSI:Biology, the next phase of the PSI program, the NESG will expand Its mission by carrying our collaborative structural genomics projects together with several PSI Consortia for High-Through-Put (HTP) Enabled Structural Biology Partnerships (Biology Partnerships) and associated Program Announcements (PARs). The primary goal of the NESG In PSI:Biology is to provide > 1,100 new 3D protein structures to the Protein Data Bank (PDB) over 5 years, together with extensive raw and processed data, protocols for sample production, structure/function annotations, and thousands of homology models derived from these structures. This will complement the ~ 900 structures deposited by NESG in PSI Phases 1 and 2. In particular, NESG will provide novel 3D structural information useful in modeling large numbers of eukaryotic and human proteins. Our efforts will span five classes of target types: (i) proteins nominated In collaborations to be established with PSI Biology Partnerships, (ii) domain families (referred to as BIG, MEGA, and META families) defined by the central PSI:Biology Target Selection Subcommittee to provide course-grained coverage of large protein domain families; (iii) proteins defined by the NESG Biomedical Theme of 'Networks of Proteins Associated with Human Cancer and Developmental Biology'; (iv) proteins nominated by the general biomedical research community, and (v) proteins selected for specific technology-development goals. Protein targets in the first two of these classes, representing ~ 80% of the overall NESG effort, will be selected in a coordinated process together with the other LSCs and Biology Partnerships so as to maximize biological impact and minimize redundant efforts. The many methods and technologies for structural genomics research developed in this project will provide the next- generation tools for traditional hypothesis-driven biological research, and will thus have powerful and broad impact on the infrastructure for biological science and engineering.