Estudios informáticos de la enzima de Trypanosoma brucei hipoxantina-guanina-xantina fosforribosiltransferasa para el uso como target de desarrollo de medicamentos

Abstract

The computer-studies conducted on the enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase from T. brucei (TbHGXPRT) as a target for drug development were docking, refinement of structures and a phylogenetic analysis. The docking process consisted of using a library of compounds (CASPeR), the purpose of the study was to determine those compounds (drugs) that are potential inhibitors of the TbHGXPRT enzyme. The result of the study determined that 381 drugs have a significant Ki and therefore can be considered as potential inhibitors. The refinement process was carried out with two specific ligands (ANPs), this refinement process provides information about the interactions that are generated between the residues of the active site and the ligand. This information was used to observe how the 20 drugs selected in the docking study are located in the active site of the TbHGXPRT enzyme. The last analysis was the phylogenetic study of the phosphoribosyltransferase (PRTases) enzyme family, in this study the alignment of the protein sequences of 30 enzymes belonging to the PRTases family of several organisms was performed. Based on the alignment, it was possible to determine those organisms that presented highly conserved waste sites and those that had variations in these sites. The study is important because the compounds selected from the docking study can be used for in vitro and in vivo tests against the parasite. In addition, the phylogenetic study will allow these compounds to be tested in other parasites that have enzymes from the PRTase family.