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

摘要

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