Structural Genomics of Eukaryotic Domain Families

描述(申请人提供)：东北结构基因组联合会(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(LSC)之一。PSI LSC的目标是：(I)利用广泛的生物、基因组和生物信息学标准，以及从特定生物主题项目中选择的目标，为大量蛋白质生成三维(3D)结构，以便对自然界中的大量蛋白质序列提供重要的结构覆盖；(Ii)开发和传播结构生物学和生物信息学的新的和/或改进的技术；以及(Iii)使这些结构、结构生产数据和相关试剂和技术向世界科学界公开。在PSI：生物，PSI计划的下一阶段，NESG将扩大其使命，与几个支持高通量(HTP)的结构生物学伙伴关系(Biology Partnership)和相关计划公告(PAR)的PSI联盟一起开展我们的协作结构基因组学项目。NESG在PSI：生物学的主要目标是在5年内向蛋白质数据库(PDB)提供1,100个新的3D蛋白质结构，以及广泛的原始和加工数据、样品生产方案、结构/功能注释以及从这些结构得出的数千个同源模型。这将补充NESG在PSI阶段1和2中沉积的~900结构。特别是，NESG将提供新的3D结构信息，有助于对大量真核和人类蛋白质进行建模。我们的工作将跨越五类目标类型：(I)将与PSI生物伙伴关系建立的合作中提名的蛋白质；(Ii)由中央PSI：生物目标选择小组委员会定义的领域家族(称为大家族、巨家族和元家族)，以提供对大型蛋白质领域家族的全程覆盖；(Iii)由Nesg Biomedical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)由一般生物医学研究界提名的蛋白质；以及(V)为特定技术开发目标选择的蛋白质。这些类别中前两类的蛋白质靶标约占总NISG工作的80%，将与其他LSC和生物伙伴关系一起在一个协调的过程中进行选择，以最大限度地增加生物影响并最大限度地减少重复的工作。本项目开发的许多结构基因组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和广泛的影响。

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.