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

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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.