In Silico Docking analysis of Mycobacterium tuberculosis potential targets AftB and EmbA withselected phytochemicals

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans, is a devastating infectious organism that kills approximately two million people annually. The current suite of antibiotics used to treat TB faces two main difficulties: (i) the emergence of multidrug-resistant (MDR) strains of M. tuberculosis, and (ii) the persistent state of the bacterium, which is less susceptible to antibiotics and causes very long antibiotic treatment regimes. It is a disease that cannot be cured through conventional remedies. Phytochemicals have played a vital role in the discovery of drugs against infectious diseases. In the current study, homology model of the targets were designed. Thirty three ligand molecules (basically secondary metabolites) which were commonly present in the plants were docked with the selected potential target of Mycobacterium tuberculosis, AftB and EmbA. The primary docking analysis was performed through iGemDock which is then validated through AutoDockVina docking software. The active sites were also predicted through the Ligand+ tool. Among all the phytochemicals palmarin had a significant inhibitory activity with both the receptors. Binding pocket for both the targets were predicted (AftB-THR 474, ASP 522, SER 524, PHE 525, LEU 526, ARG 585 and EmbA- PRO 918, ASN 924, ARG 926, VAL 1057) forming hydrogen bonds at a very low energy value, thus forming a stable complex. Palmarin had excellent conformations showing the flexible behaviour of the ligand. The total energy of the receptor and ligand complexes has also been calculated.