Probing the Molecular Mechanism of Rifampin Resistance Caused by the Point Mutations S456L and D441V on Mycobacterium tuberculosis RNA Polymerase through Gaussian Accelerated Molecular Dynamics Simulation.

ABSTRACT: Rifampin is the first-line antituberculosis drug, with Mycobacterium tuberculosis RNA polymerase as the molecular target. Unfortunately, M. tuberculosis strains that are resistant to rifampin have been identified in clinical settings, which limits its therapeutic effects. In clinical isolates, S531L and D516V (in Escherichia coli) are two common mutated codons in the gene rpoB, corresponding to S456L and D441V in M. tuberculosis However, the resistance mechanism at the molecular level is still elusive. In this work, Gaussian accelerated molecular dynamics simulations were performed to uncover the resistance mechanism of rifampin due to S456L and D441V mutations at the atomic level. The binding free energy analysis revealed that the reduction in the abilit

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC7317996 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature