01680nas a2200157   4500000000100000008004100001653001500042653001500057653001300072653002000085100001200105700001400117245011500131520126200246022001401508       2015                            d10aSimulation10aRifampicin10aM.leprae10aDrug Resistance1 aNisha J1 aShanthi V00aComputational Simulation Techniques to Understand Rifampicin Resistance Mutation (S425L) of rpoB in M. Leprae.3 a<p>M. leprae, the etiologic agent of leprosy, is non-cultivable in vitro. Consequently, the assessment of antibiotic activity against M. leprae hinge mainly upon the time consuming mouse footpad system. As M. leprae develops resistance against most of the drugs, the evolution of new long acting antimycobacterial compounds stand in need for leprosy control. The rpoB of M. leprae is the target of antimycobacterial drug, rifampicin. Recently, cases were reported that rpoB mutation (S425L) became resistant to rifampicin and the mechanism of resistance is still not well understood. The present study is aimed at studying the molecular and structural mechanism of the rifampicin binding to both native and mutant rpoB through computational approaches. From molecular docking, we demonstrated the stable binding of rifampicin through two hydrogen bonding with His420 residue of native than with mutant rpoB where one hydrogen bonding was found with Ser406. The difference in binding energies observed in the docking study evidently signifies that rifampicin is less effective in the treatment of patients with S425L variant. Moreover, the molecular dynamics studies also highlight the stable binding of rifampicin with native than mutant (S425L) rpoB.</p>
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