ENZYME FUNCTION INITIAVE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 酶功能倡议（Enzyme Function Initiative，缩写为EFI）是一个大型的、多中心的、NIH Glue资助的项目，是一个主要的推动生物学问题的项目，推动了RBVI资源和工具的开发。 该研究所的使命是开发一种基于序列/结构的强大策略，以促进发现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，这是基因组生物学的一个关键限制。这一目标将通过整合生物信息学，结构生物学，计算与酶学，遗传学和代谢组学来实现。除了一些行政和数据封装核心外，该系统还包括五个科学核心和五个桥接项目。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）的任务是作为数据分析，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（酰胺水解酶，烯醇化酶，谷氨酸转移酶，卤酸脱卤酶和类异戊二烯合酶项目），以他们各自研究的酶超家族命名，提供了这些复杂酶系统的深入实验和科学专业知识，这些酶系统构成了本书中检查的酶功能的大型测试集。 对于基因组学，Babeland实验室指导SF/Genome核心。SF/基因组核心的作用是促进开发一种通用策略，用于在功能多样的超家族中分配未知功能酶（又名未知酶）的反应和底物特异性。核心有三个目标：1）作为档案资源，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，以帮助研究人员和合作者进行目标识别，功能预测和验证。 3)对于那些已经由生物技术研究者通过实验确定了功能的酶，通过注释转移来注释这些蛋白质中每一种蛋白质中未表征的直系同源物。目前，SF/Genome核心主要集中在超家族成员的识别和亚组和家族的管理上。这项工作提供了一个大规模的背景下，有用的信息与桥接项目和其他科学核心合作的功能预测的战略。 Babeland实验室也是数据和传播核心的共同指导者。对于巴伯实验室来说，这项工作主要集中在通过实验室的网络访问数据库（结构功能链接数据库（SFLD））传播核心的使命上。支持SF/Genome Core和Data and Dissemination Core工作的许多计算资源都是由RBVI提供或支持的，而不是通过拨款资助的，例如：使用RBVI’的高性能计算集群; SFLD的存储，维护和开发;以及Cytoscape程序的开发，该程序广泛用于Babeland实验室的管理员对DNA蛋白的序列分析和注释。 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。

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.