VIRTUAL SCREENING OF FDA-APPROVED DRUGS BY MOLECULAR DOCKING AND DYNAMICS SIMULATION TO RECOGNIZE POTENTIAL INHIBITORS AGAINST MYCOBACTERIUM TUBERCULOSIS ENOYL-ACYL CARRIER PROTEIN REDUCTASE ENZYME
H. Odhar, Ahmed Fadhil Hashim, S. Ahjel, S. Humadi
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引用次数: 0
Abstract
Objective: This in silico study is aimed at identification of new possible inhibitors against Mycobacterium tuberculosis InhA enzyme by screening a library of FDA-approved drugs.
Methods: In this in silico study, a library of FDA-approved drugs was screened by molecular docking against the monomer of enoyl-acyl carrier protein reductase to recognize potential inhibitors. Then, those best drugs with minimum docking energy were subjected to molecular dynamics simulation.
Results: Out of the top ten docking hits, only revefenacin was able to maintain the closet proximity to InhA enzyme binding pocket during the two rounds of dynamics simulation. Analysis of molecular dynamics (MD) simulation data indicated that the antimuscarinic drug revefenacin has a ligand movement Root-Mean-Square Deviation (RMSD) that didn’t exceed 4 Angstrom. Also, in this MD study, revefenacin has a superior binding energy of -35.59 Kcal/mol as compared to -13.88 Kcal/mol for the other hit ergotamine. These favorable MD simulation records for revefenacin can be explained by its ability to continuously interact with enzyme binding pocket by two hydrogen bonds.
Conclusion: We report that the antimuscarinic drug revefenacin may have the potential to inhibit the enoyl-acyl carrier protein reductase for Mycobacterium tuberculosis. However, these preliminary results must be further evaluated by in vitro and in vivo studies.
期刊介绍:
International Journal of Applied Pharmaceutics (Int J App Pharm) is a peer-reviewed, bimonthly (onward March 2017) open access journal devoted to the excellence and research in the pure pharmaceutics. This Journal publishes original research work that contributes significantly to further the scientific knowledge in conventional dosage forms, formulation development and characterization, controlled and novel drug delivery, biopharmaceutics, pharmacokinetics, molecular drug design, polymer-based drug delivery, nanotechnology, nanocarrier based drug delivery, novel routes and modes of delivery; responsive delivery systems, prodrug design, development and characterization of the targeted drug delivery systems, ligand carrier interactions etc. However, the other areas which are related to the pharmaceutics are also entertained includes physical pharmacy and API (active pharmaceutical ingredients) analysis. The Journal publishes original research work either as a Original Article or as a Short Communication. Review Articles on a current topic in the said fields are also considered for publication in the Journal.