Molecular Activity of Bioactive Compounds from Mitragyna speciosa Using a Molecular Docking Approach

Abstract

Kratom (Mitragyna speciosa) is a medicinal plant that contains mitragynine, its principal alkaloid, which has been reported to interact with opioid receptors. This study aimed to evaluate the molecular interaction of mitragynine with the μ-opioid receptor (MOR) through a molecular docking approach. The three-dimensional structure of mitragynine was retrieved from the PubChem database, whereas the crystal structure of MOR was obtained from the Protein Data Bank (PDB). Molecular docking simulations were performed using PyRx, and the resulting ligand–receptor interactions were analyzed and visualized using PyMOL and BIOVIA Discovery Studio. The docking analysis yielded a binding affinity of −7.9 kcal/mol, indicating a favorable binding interaction between mitragynine and MOR. Further interaction analysis revealed that mitragynine established hydrogen bonds, hydrophobic interactions, and electrostatic interactions with several key amino acid residues located within the active binding site of MOR, including Tyr77, Gln126, Asp149, Trp295, His299, Trp320, His321, Ile324, Gly327, and Tyr328. These molecular interactions suggest that mitragynine exhibits a stable binding conformation within the MOR binding pocket, thereby supporting its potential pharmacological activity as an analgesic agent. The findings of this study provide molecular-level evidence supporting the interaction of mitragynine with MOR and contribute to the understanding of the mechanistic basis underlying the analgesic properties of Mitragyna speciosa.