Exploring molecular docking with MM-GBSA and molecular dynamics simulation to predict potent inhibitors of cyclooxygenase (COX-2) enzyme from terpenoid-based active principles of species.

Cyclooxygenase 2 (COX-2), the key enzyme involved in prostaglandin (PGs) production, is known to take part in inflammatory and immune responses. Though COX-2 inhibitors are therapeutically effective anti-inflammatory drugs, they deficit anti-thrombotic activity thus leading to increased cardiovascular diseases. Therefore, COX-2 inhibitors with improved therapeutic efficacy and tolerance are still needed. In recent years, traditional medicine systems have paid attention to the essential oil of genus , particularly for the treatment of various inflammatory illnesses, with lesser side effects. Thus, the present study aims to explore the anti-inflammatory activity of essential oil through computational-biology approaches. In this regard, virtual screening, molecular docking, and simulations were carried out on 53 compounds derived from the essential oil of species in order to provide mechanistic insights into COX-2 inhibition and identify the most actively potent anti-inflammatory compounds. Among all the docked ligands, epi-cubenol, δ-cadinene, γ-eudesmol, cubenol, and α-terpineol were found to be powerful bioactive compounds with an increased binding affinity towards COX-2 along with favorable physiochemical properties. Additionally, MD simulation in DPPC lipid bilayers was studied to examine the intrinsic dynamics and adaptability of the chosen ligands and COX-2-complexes. The findings showed that the selected five components interacted steadily with the COX-2 active site residues throughout the simulation via different bondings. The integrative-computational approach showed that the identified natural compounds may be taken into further consideration for potential and evaluation as COX-2 inhibitors, which would lead to the development of more potent and efficient anti-inflammatory drugs.Communicated by Ramaswamy H. Sarma.