Homology modeling, molecular dynamics, and molecular docking studies of Trichomonas vaginalis carbamate kinase

Carbamate kinase catalyzes the reversible reaction of carbamoyl phosphate, ADP to ATP and ammonium phosphate which is then hydrolyzed to ammonia and carbonate. In this study, the three-dimensional model of TvCK has been constructed by molecular modeling studies. The models were further energy minimized and refined. The best model was selected based on the stereochemical quality (PROCHECK, ProSA, and Verify-3D). High throughput virtual screening was carried out against TOS Lab and MayBridge database. The 10 hit compounds were selected for further rigid and flexible docking studies. The compound ID's 13288 (TOS Lab collections), 6843 and 10949 (MayBridge) show the best docking scores and binds within the predicted active site of TvCK. The in silico ADME and biological activity properties of these compounds are in acceptable range. Thus, these types of compounds could bind to the active site of TvCK. Hence, this study may play a guiding role in in vitro and in vivo studies.