In-Silico Molecular Docking Analysis of Dextromethorphan against the Human Sigma-1 Receptor

Background: The human Sigma-1 receptor is a highly conserved transmembrane protein implicated in various neurological conditions, making it a significant target for neuropharmacological intervention. Dextromethorphan, a well-known morphinan derivative, exhibits binding affinity for this receptor. Objective: This computational study aims to analyze the binding interactions and evaluate the binding affinity of Dextromethorphan at the active site of the human Sigma-1 receptor using structure-based drug design (SBDD) methodologies. Methods: In-silico molecular docking was performed utilizing PyRx (incorporating AutoDock Vina). The three-dimensional structure of the human Sigma-1 was prepared, and the ligand Dextromethorphan was optimized for docking. Post-docking visualization and analysis of protein-ligand interactions, including hydrogen bonding, hydrophobic contacts, and binding poses, were conducted using PyMOL. Result: The docking simulations revealed a favorable binding affinity of -6.8 kcal/mol for Dextromethorphan against the Sigma-1 receptor. Key interacting amino acid residues within the binding pocket were identified as [ Glu172, Asp126], which play a critical role in stabilizing the ligand-receptor complex. Conclusion: The computational analysis confirms the binding efficacy of Dextromethorphan with the Sigma-1 receptor, providing structural insights that support its pharmacological profile. These findings offer a foundational framework for further optimization and understanding of morphinan derivatives targeting the Sigma-1 receptor.