Investigation of a Stable Interaction of Levothyroxine with AFP Through Molecular Modelling

Thyroid dysfunctions are common all over the world, and accordingly, the use of thyroid drugs has increased. Incorrect measurement of tumor markers may lead to missed cases of cancer. The most used cancer markers are CA19-9, CA125, CEA, PSA, and AFP molecules. In this study, the molecular interactions of these markers with the thyroid medications of levothyroxine, methimazole, and propylthiouracil were investigated via molecular docking and dynamics simulations. In the molecular docking studies, levothyroxine was shown to interact with AFP, CEA, and CA15-3 in low concentrations. As a result of the MD simulations, the AFP/LEVO model exhibited the highest level of interaction. For instance, while the RMSD values of AFP/Levothyroxine complex were consistently around 0.7, and for the others they were observed above 1. This tight binding was reflected in interaction energies, with the total interaction in the AFP/Levothyroxine model computed as -192.04 kJ/mol. In contrast, for CA15-3/Levothyroxine and CEA/Levothyroxine complexes, these values were calculated as -135.26 and -88.56 kJ/mol, respectively. The SASA analysis also suggested the superiority of AFP/Levothyroxine complex due to ligand masking and a decrease in standard deviation, as the SASA mean difference area was found to be -0.46.