Mechanistic Insights into the Antihypertensive Effect of Resveratrol Via Inhibition of Thromboxane A2 Receptor: A Multi-Computational Approach

Resveratrol, a natural polyphenolic compound, was systematically investigated for its potential inhibitory interaction with the thromboxane A₂ receptor (TxA₂ R) using an integrated computational approach. ADMET prediction revealed favorable pharmacokinetic and safety profiles, including high intestinal absorption (98%), acceptable solubility, and absence of mutagenicity or hepatotoxicity, indicating good drug-likeness. DFT calculations confirmed the molecular stability and electronic properties conducive to receptor binding. Molecular docking identified a well-defined binding pose, stabilized by hydrogen bonds with THR81 and HIS89 and hydrophobic contacts with key residues. Subsequent 200 ns molecular dynamics simulations demonstrated structural stability of the complex, with consistent RMSD and compact Rg values. MM/GBSA analysis yielded a binding free energy of –26.09 kcal/mol, dominated by van der Waals and electrostatic interactions. Free energy decomposition highlighted ASP165, THR172, and GLY168 as principal contributors to binding. Hydrogen bond occupancy and free energy landscape analyses previous studies have shown that conformational stability and a persistent binding mode. Collectively, these findings indicate that resveratrol exhibits strong affinity and structural compatibility with the TxA₂ R, supporting its potential as a promising modulator for thromboxane A₂-mediated vascular dysfunction.