Virtual Screening and Free Energy Estimation for Identifying Mycobacterium Tuberculosis Flavoenzyme DprE1 Inhibitors

we investigated the promising MTB drug target protein, DprE1 (decaprenylphosphoryl-β-d-ribose 2’-epimerase), involve in cell was synthesis of Mycobacterium tuberculosis and plays a crucial role in host pathogenesis, virulence, lethality and survival under stress. Considering the emergence of different variants of drug resistant MTB are one of the major threats worldwide which essentially requires more effective new drug molecules with no major side effects. Here, we employed comprehensive computational methods for the structure based virtual screening of bioactive anti-tuberculosis compounds from chemical libraries ChEMBL, characterized the physicochemical properties analyses and the trajectories obtained from MD simulations were used for estimation of binding free energy, applying molecular theory of solvation (MM/PBSA, MM/GBSA AND MM/3DRISM-KH). All results were compared with known DprE1 inhibitors. Our studies suggest that four compounds (ChEMBL2441313, ChEMBL2338605, ChEMBL441373 and ChEMBL1607606) compounds may be explored as lead molecules for the rational drug designing of DprE1-inhibitors in MTB therapy.