Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies

Abstract

In the current study, we searched for potential DNA GyrB inhibitors using pharmacophorebased virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors were collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptor and hydrophobicity were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore it can be concluded that the compounds identified may have potential for the treatment of TB.