RESUMEN
BACKGROUND AND AIMS: Several studies raise concerns about the possible association of high selenium exposure with insulin resistance and type 2 diabetes. This in silico study proposes a possible mechanism of insulin resistance in the case of overexposure to selenium. METHOD: A study was carried out using molecular modeling, where cysteines of the insulin-receptor are replaced by selenocysteines. Calculation of the interaction energy of the receptor was performed in both cases with Auto Dock Tools and Vina 4.2 software to predict whether the substitution of amino acid could lead to destabilization of the protein-ligand complex and therefore possibly insulin resistance. Finally, the docked complex was analyzed by using BIOVIA Discovery Studio Visualizer to show the type of interactions between the ligands and insulin-receptor, and to determine the distance of the ligands from the binding site on insulin-receptor. RESULTS: The results show that the substitution of cysteine by selenocysteine in the insulin receptor does not lead to stabilization of the complex receptor/insulin, but to its disruption.In addition, the types and the number of bonds between insulin and its receptor in the two cases are different, where 7 strong bonds between insulin and its receptor were found in the case of the cysteine complex compared to 6 weak bonds in the second case. CONCLUSION: Findings of this study suggest that misincorporation of selenocysteines in insulin receptor could lead to destabilization of the insulin-receptor complex and therefore may possibly cause an insulin resistance.