title: Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors.
abstract: BACKGROUND
  Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order to improve its predicted binding affinity.
  
  
  RESULTS
  The proposed binding modes of the resulting compounds mimic that of ATP, the native substrate, and provide insights into novel protein-ligand interactions that may be exploited in future drug-discovery projects.
  
  
  CONCLUSIONS
  We are hopeful that these new predicted inhibitors will aid medicinal chemists in developing novel therapeutics to fight human African trypanosomiasis.
authors: Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365, USA. jdurrant@ucsd.edu
authors: Jacob D
authors: JD
authors: Durrant
authors: J Andrew
authors: JA
authors: McCammon
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019729:Carbon-Oxygen Ligases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017393:RNA Editing; D012984:Software; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: D004791:Enzyme Inhibitors; D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D019729:Carbon-Oxygen Ligases; C476580:REL1 RNA ligase, Trypanosoma brucei