3D-QSAR study of the endocrine disrupting effect of perfluorooctane sulfonates (PFOS) and perfluorooctanoic acid (PFOA) on human estrogen, androgen and thyroid receptors

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have become emerging persistent organic pollutants (POPs), but their health effects on humans remain controversial because of contradictory experimental and epidemiological studies. In this study, we used three-dimensional quantitative structure–activity relationship (3D-QSAR) method by applying Surflex-dock to study and compare the binding modes between PFOS, PFOA and eight other endocrine disrupting chemicals, and human estrogen receptor (hERα), human androgen receptor (hAR) and human thyroid receptor (hTRβ). Molecular docking and hydrogen bond studies indicated that PFOS and PFOA had high affinity potency toward hERα, hAR and hTRβ due to low free binding energies, while the highest value was obtained toward hTRβ. This means that PFOS and PFOA might have more disrupting effects on thyroid than on estrogen and androgen receptors. Hydrogen bonding interactions revealed that Met313 in hTRβ might act as the critical amino acid residue in the binding of ligand–receptor complex, which would provide an explanation for the interaction mechanisms. Our results provide an important reference and direction for the interaction mode and mechanism study between PFOS/PFOA and human endocrine systems.