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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 布鲁氏锥虫寄生虫引起非洲昏睡病，每年威胁数百万人，主要是在中部非洲最贫穷的农村人口中。目前，每年约有5-7万人受到影响。如果不治疗，这是一种致命的疾病，现有的少数几种治疗方法都有严重的副作用。迫切需要研究来开发新药。蛋白水解酶是一种分解蛋白质的酶，已被证明是“可用药”的靶标：也就是说，蛋白水解酶抑制剂已被证实是治疗艾滋病毒、糖尿病和高血压的药物。虽然预测的蛋白质序列可以从布鲁氏锥虫的整个基因组中获得，但这些数据还没有被注释为那些特定的药物靶标，比如蛋白酶。 该项目的目标是进行深入的计算分析，通过创建基于网络的视图来表征布氏锥虫的降解组，该视图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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.