Molecular Docking, Dynamics, and MM/GBSA-based Evaluation of Antidiabetic Phytoconstituents from Pterocarpus marsupium

Pterocarpus marsupium Linn bark extract has been extensively used to treat Diabetes mellitus in Ayurveda. Given the traditional claim, this study was initiated to evaluate the antidiabetic potential of the phytoconstituents in the heartwood and bark by examining their binding to targets such as Sodium glucose cotransporter-2, Dipeptidyl peptidase-4, AMP-activated protein kinase, and Aldose reductase. The docking studies were carried out using PyRx and AutoDock Vina 1.1.2 software. The binding affinities of Pteroside with Sodium glucose co-transporter-2 (-9.5 Kcal/mol), 7-O-α-L-rhamnopyranosyloxy-4′-methoxy-5-hydroxy isoflavone with Dipeptidyl peptidase-4 (-8.9 Kcal/mol), and with AMP-activated protein kinase (-8.7 Kcal/mol), and Vijayoside with Aldose reductase (-9.1 Kcal/mol) were maximum as compared to the reference cocrystallized ligand. Molecular dynamics simulation studies indicate stable binding throughout the 100 ns simulation. MM GBSA analysis elucidated the thermodynamic profile of the binding process and highlighted the key interactions governing complex stability. Among the evaluated complexes, Pteroside consistently demonstrated the strongest interaction profile with sodium glucose cotransporter-2. In view of this, clinical studies are necessary to elucidate their roles in the treatment of diabetes mellitus.