Elucidating the glucokinase activating potentials of naturally occurring prenylated flavonoids: An explicit computational approach

Kolade Olatubosun Faloye, Boris Davy Bekono, Emmanuel Gabriel Fakola, Marcus Durojaye Ayoola, Oyenike Idayat Bello, Oluwabukunmi Grace Olajubutu, Onikepe Deborah Owoseeni, Shafi Mahmud, Mohammed Alqarni, Ahmed Abdullah Al Awadh, Mohammed Merae Alshahrani, Ahmad J. Obaidullah

Research output: Contribution to journalJournal articlepeer-review

Abstract

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 glucok-inase 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.

Original languageEnglish
Article number7211
JournalMolecules
Volume26
Issue number23
DOIs
StatePublished - 1 Dec 2021

Keywords

  • ADMET
  • Density functional theory
  • Glucokinase activators
  • Molecular docking
  • Molecular dynamics simulation
  • Prenylated flavonoids

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