Computational Analysis of a Mutated μ-opioid Receptor Bound to a Morphinan Antagonist

Opium is a depressant drug, derived from the opium poppy (Papaver somniferum L.), and holds one of the earliest records of medicinal plant use. Deriva ves of opium, codeine and morphine, are extensively used in therapeu c pain relief treatments.The mu (μ) opioid receptor is produced from the OPRM1 gene and acts as the primary receptor for most opioid drugs, which are highly addic ve. Narcan is used to counter the effects of an opium overdose; if Narcan binds to the receptor more effec vely, its inhibitory effect will increase and it can bind more favorably than opium or opium deriva ves in the event of an overdose. Researchers know that differences in the receptors' structure and func on influence how the body responds to opioids. In this study, we mutated the Tryptophan-318 residue into an Arginine residue in order to observe whether it would result in a more ideal binding arrangement of narcan. We performed molecular docking in order to obtain the RMSD and affinity values for each predicted posi on of narcan with and without the inves gated muta on. On average, the Y318R μ-opioid receptor produced poses with higher binding affinity than the original protein. The op mum affinity value for the Y318R protein was also lower than that of the original protein. This led to the conclusion that muta ng Tryptophan-318 into Arginine enhances the binding of the morphinian antagonist to the μ-opioid receptor, making it more effec ve at countering the effects of an opium overdose. This research encourages further experimenta on regarding the muta on of addi onal residues and in turn the process of drug discovery can be improved.