Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis

A great challenge is posed to the treatment of tuberculosis due to the evolution of multidrug-resistant (MDR) and extensively drugresistant(XDR) strains of Mycobacterium tuberculosis in recent times. The complex cell envelope of the bacterium contains unusualstructures of lipids which protects the bacterium from host enzymes and escape immune response. To overcome the drugresistance, targeting “drug targets” which have a critical role in growth and virulence factor is a novel approach for bettertuberculosis treatment. The enzyme Phosphopantetheinyl transferase (PptT) is an attractive drug target as it is primarily involvedin post translational modification of various types-I polyketide synthases and assembly of mycobactin, which is required for lipidvirulence factors. Our in silico studies reported that the structural model of M.tuberculosis PptT characterizes the structure-functionactivity. The refinement of the model was carried out with molecular dynamics simulations and was analyzed with root meansquare deviation (RMSD), and radius of gyration (Rg). This confirmed the structural behavior of PptT in dynamic system.Molecular docking with substrate coenzyme A (CoA) identified the binding pocket and key residues His93, Asp114 and Arg169involved in PptT-CoA binding. In conclusion, our results show that the M.tuberculosis PptT model and critical CoA binding pocketinitiate the inhibitor design of PptT towards tuberculosis treatment.