Revista de bioinformática aplicada y biología computacional

Selection of Leucine as a Potential Antagonist from In Silico Analysis of ?-Opioid Receptor in the Treatment of Subjects with Herion and Opiate AddictionSelection of eucine as a Potential Antagonist

Olalekan Oladimeji, George Oche Ambrose, Uduak Umana, Olajide Olayemi, Agbon Abel and Daodu Serene

The aim of this study was to analyze the antagonistic potential of leucine on μ-opioid receptor by molecular docking studies. Studies has shown that drug addiction has reached epidemic levels across the globe with approximately 247 million drug users worldwide. Heroin binds to and activates μ-opioid receptor thereby stimulating the release of neurotransmitter dopamine, causing reinforcement of drug taking behavior. The life-threatening side effects of the current μ-opioid receptor drugs (suboxone and naloxone) such as asthenia, insomnia, rhinitis, infections, pain, headache etc. Necessitate the discovery of novel potent and safe compounds as a therapeutic approach in the treatment of drug addiction. In view of this, computational tools were adopted to out-source for better antagonist for this drug-gable target. The leucine chemical compound was retrieved from pubchem data base and was screened for its inhibitory potential on μ-opioid receptor which was retrieved from protein data bank repository. Computational docking analysis was performed using PyRx AutoDock Vina option based on scoring functions and the target was validated so as to ensure that the right target and appropriate docking protocol was used for this study. Leucine was found to have a better binding affinity with the target (-4.7 kcal/mol) when compared with the co-crystallized molecule (-2.5 kcal/mol). Leucine has a Molecular Weight (MW) of 131.174 g/mol, number of hydrogen bond donor is 2, number of hydrogen bond acceptor is 3, LogP is -1.864 and number of rotatable bond is 3. Docking studies and ADME/T (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties evaluation of leucin on μ-opioid showed that this ligand is a druggable molecule when docked well with the molecule. Therefore, Leucine plays an inhibitory role on μ-opioid receptor and thus should be implicated as a potential agent in drug addiction.