A COMPUTATIONAL ATLAS OF THE T BRUCEI DEGRADOME AS A GUIDE TO DRUG DISCOVERY

布鲁斯氏菌降解组的计算图谱作为药物发现的指南

• 批准号: 8363620
• 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
• 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/8363620
• 关键词: Active Sites; Adverse effects; Affect; African Trypanosomiasis; Amino Acid Sequence; Central Africa; Cleaved cell; Computer Analysis; Data; Diabetes Mellitus; Disease; Drug Delivery Systems; Enzymes; Funding; Genome; Goals; Grant; HIV; Hypertension; Imagery; Informatics; National Center for Research Resources; Network-based; Parasites; Peptide Hydrolases; Peptide Sequence Determination; Pharmaceutical Preparations; Principal Investigator; Protease Inhibitor; Proteins; Research; Research Infrastructure; Resources; Rural Population; Source; Structure; Trypanosoma brucei brucei; United States National Institutes of Health; base; biocomputing; computational atlas; cost; drug discovery

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 parasite Trypanosoma brucei causes African sleeping sickness and threatens millions of people per year, mostly in the poorest rural populations of Central Africa. Currently, about 50,000-70,000 people are affected per year. This is a fatal disease if untreated and the few existing treatments have serious side effects. Research is urgently needed to develop new drugs. Proteases are enzymes that cleave proteins, and have been proven to be "druggable" targets: that is, protease inhibitors have been validated as drugs to treat HIV, diabetes, and hypertension. Although predicted protein sequences are available from the entire T. brucei genome, these data have not been annotated for those that are specific drug targets, like proteases. The goals of this project are to perform an in-depth computational analysis to characterize the degradome of Trypanosoma brucei by creating network-based views based on similarities of sequence, structure, and active site motifs of T. brucei proteases.

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。 寄生虫布氏锥虫会导致非洲昏睡病，每年威胁数百万人，其中大部分是中非最贫困的农村人口。目前，每年约有 50,000-70,000 人受到影响。如果不及时治疗，这是一种致命的疾病，并且现有的少数治疗方法会产生严重的副作用。迫切需要进行研究来开发新药。蛋白酶是裂解蛋白质的酶，并已被证明是“可成药”的靶标：也就是说，蛋白酶抑制剂已被验证为治疗艾滋病毒、糖尿病和高血压的药物。尽管可以从整个布氏锥虫基因组中获得预测的蛋白质序列，但这些数据尚未针对特定药物靶点（如蛋白酶）进行注释。 该项目的目标是通过基于布氏锥虫蛋白酶的序列、结构和活性位点基序的相似性创建基于网络的视图，进行深入的计算分析，以表征布氏锥虫的降解组。