title: Designing novel inhibitors of Trypanosoma brucei.
abstract: Computational simulations of essential biological systems in pathogenic organisms are increasingly being used to reveal structural and dynamical features for targets of interest. At the same time, increased research efforts, especially from academia, have been directed toward drug discovery for neglected tropical diseases. Although these diseases cripple large populations in less fortunate parts of the world, either very few new drugs are being developed or the available treatments for them have severe side effects, including death. This chapter walks readers through a computational investigation used to find novel inhibitors to target one of these neglected diseases, African sleeping sickness (human African trypanosomiasis). Such studies may suggest novel small-molecule compounds that could be considered as part of an early-stage drug discovery effort. As an example target protein of interest, we focus on the essential protein RNA-editing ligase 1 (REL1) in Trypanosoma brucei, the causative agent of human African trypanosomiasis.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Demir
authors.forename: Rommie E
authors.initials: RE
authors.lastname: Amaro
mesh_terms: D019729:Carbon-Oxygen Ligases / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D014344:Trypanocidal Agents / Q000378:metabolism / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D024101:Mitochondrial Proteins; D014344:Trypanocidal Agents; D019729:Carbon-Oxygen Ligases; C476580:REL1 RNA ligase, Trypanosoma brucei