Structure-Based Screening of DNA GyraseB Inhibitors for Therapeutic Applications in Tuberculosis: a Pharmacoinformatics Study
Islam, Pranjali Mahadeo Tambe & Shovonlal Bhowmick & Sushil K. Chaudhary & Mohammad Rizwan Khan & Saikh M. Wabaidur & Mohd. Muddassir & Preeti Chunarkar Patil & Md Ataul . 2020
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) and
considered as serious public health concern worldwide which kills approximately five thousand
people every day. Therefore, TB drug development efforts are in gigantic need for
identification of new potential chemical agents to eradicate TB from the society. The bacterial
DNA gyrase B (GyrB) protein as an experimentally widely accepted effective drug target for
the development of TB chemotherapeutics. In the present study, advanced
pharmacoinformatics approaches were used to screen the Mcule database against the GyrB
protein. Based on a number of chemometric parameters, five molecules were found to be
crucial to inhibit the GyrB. A number of molecular binding interactions between the proposed
inhibitors and important active site residues of GyrB were observed. The predicted druglikeness
properties of all molecules were indicated that compounds possess characteristics to
be the drug-like candidates. The dynamic nature of each molecule was explored through the
molecular dynamics (MD) simulation study. Various analyzing parameters from MD simulation
trajectory have suggested rationality of the molecules to be potential GyrB inhibitor.
Moreover, the binding free energy was calculated from the entire MD simulation trajectories
highlighted greater binding free energy values for all newly identified compounds also
substantiated the strong binding affection towards the GyrB in comparison to the novobiocin.
Therefore, the proposed molecules might be considered as potential anti-TB chemical agents
for future drug discovery purposes subjected to experimental validation.
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