In silico screening and molecular dynamics simulations study to identify novel potent inhibitors against Mycobacterium tuberculosis DnaG primase

Abstract

Tuberculosis remains a major global health threat killing millions of people. Due to existing multiple drug resistance (MDR) and prolonged treatment it becomes necessary to explore novel drug targets in Mycobacterium tuberculosis (Mtb). DnaG primase, having a significant role in primer synthesis during initiation of DNA replication, has emerged as a promising drug target. The three dimensional (3D) model of its catalytic domain (Toprim) was constructed. Further, in silico screening of the three diverse chemical compound libraries against the modeled domain was carried out. Four top screened compounds were identified and evaluated by ADMET analysis. The stability of these compounds in complex with the Toprim domain was validated through 50 ns molecular dynamics simulations. Lys 101, Glu 137 and Asp 188 in the active site predominantly formed the hydrogen bonds with the top screened compounds. Hence, the drug-like compounds identified can be taken up for the further experimental investigation as anti-tubercular agents.