Flavanones: A potential natural inhibitor of the ATP binding site of PknG of Mycobacterium tuberculosis
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Drug resistance, Drug-likeness, Flavanones, Hydrophobic pocket, Molecular docking, Molecular dynamics simulation, Mycobacterium tuberculosis, PknG,
- MeSH
- Adenosine Triphosphate metabolism MeSH
- Bacterial Proteins chemistry MeSH
- Mycobacterium tuberculosis * metabolism MeSH
- Cyclic GMP-Dependent Protein Kinases chemistry metabolism MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Binding Sites MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- Bacterial Proteins MeSH
- Cyclic GMP-Dependent Protein Kinases MeSH
Over the years, Mycobacterium tuberculosis has been one of the major causes of death worldwide. As several clinical isolates of the bacteria have developed drug resistance against the target sites of the current therapeutic agents, the development of a novel drug is the pressing priority. According to recent studies on Mycobacterium tuberculosis, ATP binding sites of Mycobacterium tuberculosis serine/threonine protein kinases (MTPKs) have been identified as the new promising drug target. Among the several other protein kinases (PKs), Protein kinase G (PknG) was selected for the study because of its crucial role in modulating bacterium's metabolism to survive in host macrophages. In this work, we have focused on the H37Rv strain of Mycobacterium tuberculosis. A list of 477 flavanones obtained from the PubChem database was docked one by one against the crystallized and refined structure of PknG by in-silico techniques. Initially, potential inhibitors were narrowed down by preliminary docking. Flavanones were then selected using binding energies ranging from -7.9 kcal.mol-1 to -10.8 kcal.mol-1. This was followed by drug-likeness prediction, redocking analysis, and molecular dynamics simulations. Here, we have used experimentally confirmed drug AX20017 as a reference to determine candidate compounds that can act as potential inhibitors for PknG. PubChem165506, PubChem242065, PubChem688859, PubChem101367767, PubChem3534982, and PubChem42607933 were identified as possible target site inhibitors for PknG with a desirable negative binding energy of -8.1, -8.3, -8.4, -8.8, -8.6 and -7.9 kcal.mol-1 respectively. Communicated by Ramaswamy H. Sarma.
Department of Botany St Joseph's College Bangalore Karnataka India
Department of Chemistry Federal Institute of Espirito Santo Unit Vila Velha Vila Velha ES Brazil
Independent Researcher Karnataka Bangalore India
Laboratory of Computational Chemistry Department of Chemisry UFLA Lavras MG Brazil
PPGQUI Federal University of Espirito Santo Vitoria ES Brazil
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