Computational saturation mutagenesis to predict structural consequences of systematic mutations in the beta subunit of RNA polymerase in <i>Mycobacterium leprae</i>.

ABSTRACT: Rifampin resistance in leprosy may remain undetected due to the lack of rapid and effective diagnostic tools. A quick and reliable method is essential to determine the impacts of emerging detrimental mutations in the drug targets. The functional consequences of missense mutations in the β-subunit of RNA polymerase (RNAP) in Mycobacterium leprae (M. leprae) contribute to phenotypic resistance to rifampin in leprosy. Here, we report in-silico saturation mutagenesis of all residues in the β-subunit of RNAP to all other 19 amino acid types (generating 21,394 mutations for 1126 residues) and predict their impacts on overall thermodynamic stability, on interactions at subunit interfaces, and on β-subunit-RNA and rifampin affinities (only for the rifampin binding site) using

SUBMITTER: Vedithi SC 

PROVIDER: S-EPMC7000446 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature