ENZYME FUNCTION INITIAVE

酶功能倡议

基本信息

批准号：
8363638
负责人：
PATRICIA CLEMENT BABBITT
金额：
$ 1.68万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8363638
关键词：
Amidohydrolases Annual Reports Archives Automobile Driving Bioinformatics Biological Biology Collaborations Data Data Analyses Data Storage and Retrieval Databases Development Enzymatic Biochemistry Enzymes Family Funding Genetic Genome Genomics Glues Glutathione S-Transferase Goals Grant Imagery In Vitro Informatics Maintenance Metabolic Microbiology Mission Multienzyme Complexes Names National Center for Research Resources Orthologous Gene Performance Physiological Principal Investigator Proteins Reaction Research Research Infrastructure Research Personnel Resource Development Resources Role Sequence Analysis Source Structure Subgroup Substrate Specificity System Testing United States National Institutes of Health Update Validation Work base biocomputing computing resources cost database structure enolase haloacid dehalogenase in vivo isoprenoid member metabolomics programs structural biology tool web-accessible

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Enzyme Function Initiative (EFI) is a large, multi-center, NIH Glue grant funded project that is a major driving biological problem motivating the development of resources and tools at the RBVI. The mission of the EFI is to develop a robust sequence/structure-based strategy for facilitating discovery of in vitro enzymatic and in vivo metabolic/physiological functions of unknown enzymes discovered in genome projects, a crucial limitation in genomic biology. This goal will be accomplished by integrating bioinformatics, structural biology, and computation with enzymology, genetics, and metabolomics. The EFI is composed of five scientific cores and five bridging projects in addition to some administrative and data encapsulation cores. The scientific cores (Superfamily (SF)/Genome, Protein, Computation, Structure and Microbiology Core) are tasked with being central resources for data analysis, structure determination, high-throughput experimentation and data storage. The five bridging projects (Amidohydrolase, Enolase, Glutathione Transferase, Haloacid Dehalogenase and Isoprenoid Synthase Project), named for the enzyme superfamilies they each study, provide in depth experimentation and scientific expertise in these complex enzyme systems that make up the large test set of enzyme functions examined in the EFI. For the EFI, the Babbitt lab directs the SF/Genome core. The role of the SF/Genome Core is to contribute to the development of a general strategy for assignment of reaction and substrate specificity for enzymes of unknown function, aka “unknowns,” in functionally diverse superfamilies. The core has three aims: 1) Serve as an archive resource, maintaining sequence, structural and functional data. 2) In collaboration with the Bridging Projects and the other Scientific Cores, computationally analyze these SFs to aid in target identification, function prediction, and validation by EFI investigators and collaborators. 3) For enzymes for which the functions have been experimentally established by EFI investigators, annotate uncharacterized orthologs in each of these proteins by annotation transfer. Currently, the SF/Genome core is focused principally on identification of superfamily members and curation into subgroups and families. This work provides a large-scale context useful for informing a strategy for function prediction in collaboration with the Bridging Projects and other Scientific Cores. The Babbitt lab is also co-directs the Data and Dissemination Core. For the Babbitt lab this work focuses mostly on the dissemination mission of the core through the lab’s web accessible database, the Structure Function Linkage Database (SFLD). Many of the computational resources underpinning the work of both the SF/Genome Core and the Data and Dissemination Core are supplied by or supported by the RBVI and are not funded through the EFI grant, for example: the use of the RBVI’s high performance computation cluster; the storage, maintenance, and development of the SFLD; and the development of the Cytoscape program used extensively for sequence analysis and annotation by currators in the Babbitt lab for EFI proteins. Recent progress of this work is presented in the updates for the Cytoscape and the SFLD projects within this annual report.

该子项目是利用资源的众多研究子项目之一由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持并且子项目的主要研究者可能是由其他来源提供的，包括其他 NIH 来源。子项目可能列出的总成本代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。酶功能计划 (EFI) 是一个大型、多中心、由 NIH Glue 资助的项目，是推动 RBVI 资源和工具开发的主要驱动生物学问题。 EFI 的使命是开发一种强大的基于序列/结构的策略，以促进基因组计划中发现的未知酶的体外酶促和体内代谢/生理功能的发现，这是基因组生物学的一个关键限制。这一目标将通过将生物信息学、结构生物学和计算与酶学、遗传学和代谢组学相结合来实现。 EFI 由五个科学核心和五个桥接项目以及一些管理和数据封装核心组成。科学核心（超家族（SF）/基因组、蛋白质、计算、结构和微生物学核心）的任务是成为数据分析、结构测定、高通量实验和数据存储的中心资源。五个桥接项目（酰胺水解酶、烯醇化酶、谷胱甘肽转移酶、卤酸脱卤酶和类异戊二烯合酶项目）以其各自研究的酶超家族命名，为这些构成大型酶测试集的复杂酶系统提供了深入的实验和科学专业知识。 EFI 中检查的功能。对于 EFI，Babbitt 实验室负责 SF/Genome 核心。 SF/基因组核心的作用是促进制定通用策略，以分配功能多样的超家族中功能未知的酶（又称“未知物”）的反应和底物特异性。该核心具有三个目标： 1）充当档案资源，维护序列、结构和功能数据。 2) 与桥接项目和其他科学核心合作，通过计算分析这些 SF，以帮助 EFI 研究人员和合作者进行目标识别、功能预测和验证。 3) 对于 EFI 研究人员已通过实验确定其功能的酶，通过注释转移注释每个蛋白质中未表征的直向同源物。目前，SF/基因组核心主要侧重于超家族成员的识别以及亚组和家族的管理。这项工作提供了一个大规模的背景，有助于为与桥接项目和其他科学核心合作的功能预测策略提供信息。巴比特实验室还共同领导数据和传播核心。对于巴比特实验室来说，这项工作主要侧重于通过实验室的网络可访问数据库——结构函数链接数据库（SFLD）来传播核心的任务。支持 SF/基因组核心和数据和传播核心工作的许多计算资源均由 RBVI 提供或支持，而不是通过 EFI 拨款资助，例如：使用 RBVI 的高性能计算集群; SFLD 的存储、维护和开发；以及 Cytoscape 程序的开发，广泛用于 Babbitt 实验室 EFI 蛋白质的序列分析和注释。本年度报告中 Cytoscape 和 SFLD 项目的最新进展介绍了这项工作的最新进展。