Exploring Therapeutic Insights: Computational Docking Analysis of 5HTR2A Protein Structure involved in Temporomandibular Joint Disorders

INTRODUCTION: Dysregulated HTR2A receptor function and serotonin signaling pathways can contribute to TMJ disorders, underscoring the significance of comprehending structural variations in the HTR2A gene protein for pioneering therapeutic strategies. This study aims to explore the molecular interactions between HTR2A receptor and potential therapeutic ligands via computational docking, aiming to pinpoint innovative targets for intervening pain in TMJ disorders. METHODS: A virtual screening of 100 candidate compounds was performed based on drug-likeness, molecular docking scores, and ADMET profiles. The 3D structure of the HTR2A receptor was retrieved (PDB ID: 6A94), and docking simulations were conducted using AutoDock Vina and BIOVIA Discovery Studio. Pharmacophore models were generated using LigandScout, and key ligands were analyzed using PyRx, PyMOL, and pkCSM tools. RESULTS: The PyRx molecular docking analysis identified two novel compounds, 2,5-Dimethoxy-4-iodoamphetamine and 2,5-dimethoxy-4-methylamphetamine, displaying robust binding affinities with the HTR2A gene in comparison to conventional compounds. In addition, these newly identified compounds satisfied stringent pharmaceutical criteria, meeting criteria such as Lipinski's Rule, Ghose's Rule, Veber's Rule, Egan's Rule, and Muegge's Rule, suggesting their potential as promising therapeutic options for treating TMJ disorders. CONCLUSION: The study highlights the strong binding affinity between the 5HTR2A gene and novel compounds, suggesting their potential as effective therapeutic agents for TMJ disorders, with promising pharmacokinetic profiles and implications for advancing computational drug discovery in medical research.