In silico screening for apstatin probestin and bestatin as new trypanocidal compounds inhibiting trypanosoma brucei brucei tricorn interacting factor 3 homologs

Abstract

Trypananosoma brucei brucei causes African Trypanosomiasis (AT), a neglected tropical disease affecting both humans and animals.Various classes of T.b. brucei peptidases have been studied and implicated as virulence factors, examples include Tricorn interacting factor 3 (F-3). This study was conducted with an objective of identifying potential trypanocidal compounds inhibiting T. b. brucei Tricorn interacting factor F-3 through ligand and structure based virtual screening. Three dimensional (3D) structure of Trf 3 enzyme was downloaded from Protein Data Bank (PDB format). All the potential ligands for the enzyme were downloaded from PubChem.  Docking simulation was carried out using the AutoDock 4.0 suite as molecular-docking tool. The top 10 poses for each test ligand were noted and the best conformer/pose for each identified as their respective final results. Based on the docking results generated, all the compounds showed good binding energy toward the target protein whereby Apstatin, Probestin and Bestatin presented the best minimum docking score of −8.17, −8.04 and −6.83 KCal mol−1, respectively. These 3 compounds strongly interacted with several amino acid residues of the active site of enzymes Glu266, Glu233, Glu288, His265 and Met232.  Therefore; Apstatin,  robestin and  Bestatin  compounds  were  presented  as  potential trypanocidal compounds that can further be investigated through in vivo or in vitro studies to validate them as potential drug molecules against African trypanosomias.