Abstract
The human exposure to diverse endocrine-disrupting chemicals (EDCs) has increased dramatically over several decades with very adverse health effects. Plasticizers and flame retardants constitute important classes of EDCs interfering in endocrine physiology including the thyroid function. Thyroxine (T4) is an important hormone regulating metabolism and playing key roles in developmental processes. In this study, six phthalate and nonphthalate plasticizers and one flame retardant (BDE-153) were subjected to structural binding against thyroxine-binding globulin (TBG). The aim was to understand their potential role in thyroid dysfunction using structural binding approach. The structural study was performed using Schrodinger's induced fit docking, followed by binding energy estimations of ligands and the molecular interaction analysis between the ligands and the amino acid residues in the TBG ligand-binding pocket. The results indicated that all the compounds packed tightly into the TBG ligand-binding pocket with similar binding pattern to that of TBG native ligand, T4. A high majority of TBG interacting amino acid residues for ligands showed commonality with native ligand, T4. The estimated binding energy values were highest for BDE-153 followed by nonphthalate plasticizer, DINCH, with values comparable with native ligand, T4. The estimated binding energy values of other plasticizers DEHP, DEHT, DEHA, ATBC, and TOTM were less than DINCH. In conclusion, the tight docking conformations, amino acid interactions, and binding energy values of the most of the indicated ligands were comparable with TBG native ligand, T4, suggesting their potential for thyroid dysfunction. The results revealed highest potential thyroid disruptive action for BDE-153 and DINCH.