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。 寄生虫锥虫布鲁氏菌会引起非洲昏昏欲睡的疾病，并威胁到每年数百万的人，主要是中非最贫穷的农村人口。目前，每年约有50,000-70,000人受到影响。如果未经治疗，少数现有治疗方法具有严重的副作用，这是一种致命的疾病。迫切需要研究新药。蛋白酶是裂解蛋白质的酶，已被证明是“可药的”靶标：也就是说，蛋白酶抑制剂已被验证为治疗HIV，糖尿病和高血压的药物。尽管可以从整个T. brucei基因组中获得预测的蛋白质序列，但对于特定药物靶标，例如蛋白酶，这些数据尚未注释这些数据。 该项目的目标是执行深入的计算分析，以基于基于网络的视图，基于序列，结构和主动位点的相似性来表征Brucei锥虫的降解组。