Utilizing Molecular Docking and Mutagenesis of Lys-233 into Ala-233 to Analyze the Effect on the Binding of the Morphinian Antagonist to the μ-Opioid Receptor

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Opium is one of the oldest known medicines. Its derivatives, morphine and codeine, are among the most utilized therapeutic treatments to relieve severe pain (Manglik et al., 2012). Opium was originally used to create the first crystal structure of the μ-opioid receptor: the primary receptor for opioids that regulate the body’s response to pain (MedlinePlus, 2021). However, a method to increase the binding efficiency of its morphinian antagonist, β-funaltrexamine (β-FNA), is still unknown. In this study the residue, Lys-233, was mutated into Ala-233 to observe significant changes to binding. We used computational tools including AutoDock Vina (Eberhardt et al., 2021; Trott, et al., 2010) and PyMOL (The PyMOL Molecular Graphics System) to redock the ligand into the mutated protein. As a result, we found that the best RMSD value before mutation was 1.87 Å, but after mutation became 1.167 Å. On average, in the series of trials that occurred after the mutation, the nine poses produced better RMSD values. This led to the conclusion that mutating Lys-233 into Ala-233 enhances the binding of the morphinian antagonist to the μ-opioid receptor. Such research encourages the mutation of other opioid receptor residues in order to anticipate which variation provides the optimal result. This study suggests that many other combinations of mutations exist, through which the process of drug discovery can be improved.