Predictive Binding Affinity of Plant-Derived Natural Products Towards the Protein Kinase G Enzyme of Mycobacterium tuberculosis (MtPknG)
Authors
Rana Qasaymeh
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK; [email protected] (R.M.Q.); [email protected] (D.R.)
Dino Rotondo
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK; [email protected] (R.M.Q.); [email protected] (D.R.)
Carel Oosthuizen
Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa; [email protected] (C.B.O.); [email protected] (N.L.)
Namrita Lall
Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa; [email protected] (C.B.O.); [email protected] (N.L.)
Veronique Seidel
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK; [email protected] (R.M.Q.); [email protected] (D.R.)
Keywords:
AutoDock Vina, flavonoids, molecular docking, Mycobacterium tuberculosis, Pelargonium reniforme, Pelargonium sidoides, Protein kinase G (PknG), SiteMap
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a growing public health concern worldwide, especially with the emerging challenge of drug resistance to the current drugs. Efforts to discover and develop novel, more effective, and safer anti-TB drugs are urgently needed. Products from natural sources, such as medicinal plants, have played an important role in traditional medicine and continue to provide some inspiring templates for the design of new drugs. Protein kinase G, produced by M. tuberculosis (MtPKnG), is a serine/threonine kinase, that has been reported to prevent phagosome-lysosome fusion and help prolong M. tuberculosis survival within the host’s macrophages. Here, we used an in silico, target-based approach (docking) to predict the interactions between MtPknG and 84 chemical constituents from two medicinal plants (Pelargonium reniforme and Pelargonium sidoides) that have a well-documented historical use as natural remedies for TB. Docking scores for ligands towards the target protein were calculated using AutoDock Vina as the predicted binding free energies. Ten flavonoids present in the aerial parts of P. reniforme and/or P. sidoides showed docking scores ranging from −11.1 to −13.2 kcal/mol. Upon calculation of all ligand efficiency indices, we observed that the (−ΔG/MW) ligand efficiency index for flavonoids (4), (5) and (7) was similar to the one obtained for the AX20017 control. When taking all compounds into account, we observed that the best (−ΔG/MW) efficiency index was obtained for coumaric acid, coumaraldehyde, p-hydroxyphenyl acetic acid and p-hydroxybenzyl alcohol. We found that methyl gallate and myricetin had ligand efficiency indices superior and equal to the AX20017 control efficiency, respectively. It remains to be seen if any of the compounds screened in this study exert an effect in M. tuberculosis-infected macrophages.
Keywords: AutoDock Vina, flavonoids, molecular docking, Mycobacterium tuberculosis, Pelargonium reniforme, Pelargonium sidoides, Protein kinase G (PknG), SiteMap
Author Biography
Namrita Lall, Department of Plant and Soil Sciences, University of Pretoria, Pretoria 0002, South Africa; [email protected] (C.B.O.); [email protected] (N.L.)
College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka 570015, India
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