In Silico Elucidation of the Binding Mechanisms and Molecular Dynamics of Oroxylin A -2,3-Dioxygenase Interaction: An Insight into Therapeutic Potentiation of Quercetin’s Cardioprotection.

Abstract

Elucidating the intricate interplay between enzymes and natural compounds is essential for designing therapeutic strategies. This study employs advanced computational techniques to explore the binding mechanisms between quercetin 2,3-dioxygenase (QDO) and oroxylin A, revealing specific interaction patterns and key residues crucial to the formation of the QDO-oroxylin A complex. Molecular docking simulations revealed a favorable binding affinity (docking score: -5.6 kcal/mol) between Oroxylin A and the active site cavity of QDO, which was supported by Oroxylin A's specific orientation (Pose 3). Despite an observed RMSD value of 2.776 indicating a moderate deviation between the docked pose and the reference structure, the formation of two hydrogen bonds with GLN 93 chain D underscores specific molecular interactions driving the binding process. This hydrogen bond formation suggested the presence of a stable and specific binding mode between Oroxylin A and QDO, likely influencing the functional dynamics of the enzyme, necessitating further refinement and validation of the docking model. The ensuing deliberation on the implications of Oroxylin A include its potential as a modulator of QDO activity, emphasizing the importance of molecular-level insights in comprehending enzyme-compound interactions. Oroxylin A, a quercetin 2,3-dioxygenase inhibitor, was used in combination with other agents to prolong the biological impacts of quercetin, thereby amplifying its antioxidant and anti-inflammatory effects. This strategic approach exhibits promise in augmenting cardioprotective benefits, immune system support, and protection against diverse pathological conditions. Subsequent considerations of dosage, bioavailability, and healthcare professional consultation are imperative for judicious supplementation, particularly in individuals with prevailing health conditions or medications. This ongoing in silico study is dedicated to revealing the potential synergistic interactions of Oroxylin A, potentiating the long-term effects of quercetin and advancing our understanding of these intricacies.