Structure-based virtual screening approach for identifying DNA gyrase inhibitors of mycobacterium tuberculosis

Abstract

To combat drug resistance tuberculosis, new drugs and methodologies are emerging. The present study focuses on identifying new chemical entity with potent DNA gyrase inhibitory activity. DNA gyrase is a type II topoisomerase enzyme, which encodes two subunits namely gyrA and gyrB, former contains tyrosine active site, which is essential for cleavage and relegation of DNA, while the latter is required for ATP hydrolysis. A small library of 485 compounds were designed and docked into DNA gyrase core in order to identify the potential inhibitor against target enzyme. Molecular docking was performed by using Glide. The crystal structures of the target were retrieved from RCSB PDB. The docking was performed by 3 modes namely HTVS, SP and XP. Prime MM-GBSA was used to calculate binding affinity and energy interactions are studied and hydrogen bond distance was calculated. All the designed compounds showed significant activity with A34 and A232 displaying maximum binding score.