ENZYME FUNCTION INITIAVE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 酶功能倡议(EFI)是一个大型的、多中心的、由NIH胶水赠款资助的项目，它是一个主要的推动生物学问题的项目，激励着RBVI资源和工具的开发。EFI的任务是开发一种强大的基于序列/结构的策略，以促进发现基因组计划中发现的未知酶的体外酶功能和体内代谢/生理功能，这是基因组生物学中的一个关键限制。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梁项目组成，此外还有一些管理和数据封装核心。科学核心(超家族/基因组、蛋白质、计算、结构和微生物核心)的任务是成为数据分析、结构确定、高通量实验和数据存储的中心资源。这五个桥接项目(氨基水解酶、烯醇酶、谷胱甘肽转移酶、卤酸脱卤酶和类异戊二烯合成酶项目)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，这些复杂的酶系统构成了EFI检查的酶功能的大型测试集。 对于EFI，巴比特实验室负责指导SF/Genome核心。SF/基因组核心的作用是为功能不同的超家族中未知功能的酶的反应和底物专一性的一般策略的制定做出贡献。核心有三个目的：1)作为档案资源，维护有序、结构和功能数据。2)与桥接项目和其他科学核心合作，对这些SF进行计算分析，以帮助EFI调查人员和合作者识别目标、预测功能和验证。3)对于EFI研究人员已经通过实验确定其功能的酶，通过注释转移来注释每个蛋白质中的未表征的同源基因。目前，SF/Genome核心主要集中于超家族成员的识别和亚组和家族的管理。这项工作提供了一个大范围的背景，有助于为与桥梁项目和其他科学核心合作的功能预测战略提供信息。 巴比特实验室也是数据和传播核心的联合导演。对于巴比特实验室，这项工作主要集中在通过实验室的核心传播任务&S网络可访问数据库，结构功能联动数据库。支持科学/基因组核心以及数据和传播核心工作的许多计算资源都是由RBVI提供或支持的，而不是通过EFI赠款提供的，例如：使用RBVI&8217；S高性能计算集群；SFLD的存储、维护和开发；以及开发Cytoscape程序，广泛用于巴比特实验室EFI蛋白质的收银员进行序列分析和注释。这项工作的最新进展载于本年度报告中关于Cytoscape和SFLD项目的最新情况。

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.