Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
| Autor: | Mohammed H. Alqarni, Shafi Mahmud, Boris Davy Bekono, Oyenike Idayat Bello, Kolade Olatubosun Faloye, Onikepe Deborah Owoseeni, Emmanuel Gabriel Fakola, Mohammed Merae Alshahrani, Oluwabukunmi Grace Olajubutu, Marcus Durojaye Ayoola, Ahmad J. Obaidullah, Ahmed Abdullah Al Awadh |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Stereochemistry
Allosteric regulation prenylated flavonoids Pharmaceutical Science Enzyme Activators Organic chemistry Article Analytical Chemistry Molecular dynamics QD241-441 Prenylation Catalytic Domain Drug Discovery Glucokinase glucokinase activators Humans Physical and Theoretical Chemistry density functional theory chemistry.chemical_classification Flavonoids Virtual screening biology Active site molecular docking In vitro Molecular Docking Simulation molecular dynamics simulation ADMET Enzyme chemistry Chemistry (miscellaneous) biology.protein Molecular Medicine |
| Zdroj: | Molecules, Vol 26, Iss 7211, p 7211 (2021) Molecules Molecules; Volume 26; Issue 23; Pages: 7211 |
| ISSN: | 1420-3049 |
| Popis: | Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials. |
| Databáze: | OpenAIRE |
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