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）资助的四个大规模结构生产中心（LSC）之一。PSI LSC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以及从特定生物学主题项目中选择的靶标生成三维（3D）结构，以便提供大量蛋白质序列的显著结构覆盖。（ii）开发和传播结构生物学和生物信息学的新技术和/或改进技术，（iii）向全世界科学界公开提供这些结构、结构生产数据以及相关试剂和技术。在PSI：生物学，PSI计划的下一阶段，NESG将通过与几个PSI联盟一起开展我们的合作结构基因组学项目来扩大其使命，这些项目是高通量（HTP）结构生物学伙伴关系（生物学伙伴关系）和相关的计划公告（PAR）。NESG In PSI：Biology的主要目标是在5年内向蛋白质数据库（PDB）提供超过1，100个新的3D蛋白质结构，以及大量的原始和处理数据、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阶段1和2中沉积的约900个结构。特别是，NESG将提供新的三维结构信息，可用于模拟大量的真核生物和人类蛋白质。我们的努力将跨越五类目标类型：（i）与PSI生物学合作伙伴关系建立的合作中提名的蛋白质，（ii）结构域家族（iii）由“与人类癌症和发育生物学相关的蛋白质网络”的NESG生物医学主题定义的蛋白质;（iv）一般生物医学研究团体提名的蛋白质，以及（v）为特定技术开发目标选择的蛋白质。这些类别中的前两类蛋白质目标占NESG总体工作的约80%，将与其他LSC和生物学伙伴关系一起在协调过程中选择，以最大限度地提高生物影响并最大限度地减少冗余工作。该项目开发的结构基因组学研究的许多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，因此将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.