Comparative computer-based docking analysis of quercetin targeting protein tyrosine phosphatase 1B as a potential antidiabetic agent

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling and represents an attractive therapeutic target for type 2 diabetes. In this study, the binding potential of quercetin, a natural flavonoid, toward PTP1B was evaluated using molecular docking. A precisely defined grid box encompassing the catalytic pocket ensured accurate exploration of ligand conformations. Docking simulations using Auto Dock Vina identified a top-ranked binding pose with a binding affinity of −7.2 kcal/mol, supported by RMSD values of 0 Å, indicating a highly stable and well-converged orientation. Quercetin formed multiple hydrogen bonds with essential residues (ARG112, GLN123, THR154, SER151, ARG156), along with hydrophobic interactions involving ILE149 and VAL113. A significant π–cation interaction with HIS175 further contributed to ligand stabilization within the catalytic site. These interactions collectively highlight quercetin’s strong binding complementarity and support its potential as a PTP1B inhibitor. The findings align with previous reports demonstrating quercetin’s role in improving insulin sensitivity. Overall, the computational results suggest that quercetin may serve as a promising natural inhibitor of PTP1B; however, further experimental validation is necessary to confirm its therapeutic relevance.