In silico study identifies plant isoflavonoids as potent PPAR-γ agonists, suggesting safer natural therapeutic candidates for type 2 diabetes mellitus.
Key Points
Identify novel, safer natural PPAR-γ agonists among dietary isoflavonoids to avoid the adverse side effects associated with conventional thiazolidinediones.
Screened 19 FooDB isoflavonoids against PPAR-γ (PDB: 3DZY) using Glide SP docking and structural interaction fingerprint (SIFt) validation.
Characterized electronic properties using density functional theory (DFT) and predicted pharmacokinetic and bioactivity parameters through ADMET and PASS profiling.
Assessed dynamic complex stability and binding free energy using 100-ns molecular dynamics (MD) simulations and MM-GBSA calculations.
Genistin and daidzin were identified as primary lead compounds, with docking scores of −10.837 kcal/mol and −10.125 kcal/mol, respectively.
Genistin exhibited high electronic stability with a HOMO-LUMO gap of 7.80 eV and favorable drug-likeness with 58% predicted human intestinal absorption.
Molecular dynamics confirmed a stable PPAR-γ complex with genistin, maintaining persistent hydrogen bonds with HIS435 (91%) and LEU325 (94%) alongside an MM-GBSA binding free energy of −60 kcal/mol.