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.

该副本是利用资源的众多研究子项目之一由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持而且，副投影的主要研究员可能是其他来源提供的包括其他NIH来源。列出的总费用可能代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。酶功能倡议（EFI）是一个大型的，多中心的NIH胶水赠款资助的项目，是一个主要的驱动生物学问题，激发了RBVI的资源和工具的开发。 EFI的使命是开发一种基于强大的序列/结构策略，以促进在基因组项目中发现的未知酶的体外酶促和体内代谢/生理功能，这是基因组生物学的关键限制。该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除了一些行政和数据封装核心外，还由五个科学核心和五个桥接项目组成。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）的任务是用于数据分析，结构确定，高通量实验和数据存储的中心资源。五个桥接项目（氨基氢化酶，烯醇酶，谷胱甘肽转移酶，卤酸脱核酶和异丙型合酶项目）以它们各自研究的酶超家族命名，在这些复杂的酶系统中提供了深入的实验和科学专业知识，可在这些复杂的酶系统中构成Enzeme函数的大型测试。对于EFI，Babbitt实验室指导SF/基因组核心。 SF/基因组核心的作用是为未知功能的酶（又称“未知数”）在功能多样的超级家族中的酶（又称“未知数”）的反应和底物特异性的一般策略做出贡献。核心具有三个目的：1）作为存档资源，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，计算分析这些SF，以帮助EFI调查人员和合作者的目标识别，功能预测和验证。 3）对于EFI研究者实验建立了功能的酶，通过注释转移来注释这些蛋白质中的每个蛋白质中的直系同源物。目前，SF/基因组核心主要集中在识别超家族成员并策划为子组和家庭中。这项工作为与桥接项目和其他科学核心合作的策略提供了为功能预测的策略提供有用的大规模背景。 Babbitt实验室还与数据和传播核心共同指导。对于Babbitt实验室，这项工作主要集中在核心通过实验室访问数据库（结构函数链接数据库（SFLD））的传播任务上。支持SF/Genome Core和数据和传播核心的工作的许多计算资源都是由RBVI提供或支持的数据和传播核心，并且不是通过EFI赠款资助的，例如：使用RBVI的高性能计算集群； SFLD的存储，维护和开发； Cytoscape程序的开发广泛用于EFI蛋白的Babbitt Lab中弯曲器的序列分析和注释。这项工作的最新进展是在本年度报告中的Cytoscape和SFLD项目的更新中提出的。