Perfluorinated compounds binding to estrogen receptor of different species: a molecular dynamic modeling

Perfluorinated compounds (PFCs) were widely utilized in commercial and industrial applications, which could interfere with the endocrine systems of experimental animals and humans by interacting with estrogen receptors (ERs). Considering the possible differential binding preferences and relative binding affinities of PFCs to ERs of humans and other species, a cross-species comparison is necessary to effectively assess the health risk of PFCs to humans. In the present work, the species-specific binding characterizations between two PFCs, including perfluorooctane sulfonate (PFOS) and PFOS(4m, 5m), and the different ERs from Rattus norvegicus, rainbow trout, and humans were explored based on a molecular dynamic modeling. The results proved that linear perfluorinated compound PFOS could make a much stronger binding to ER alpha s than the branched perfluorinated compounds PFOS(4m, 5m). In addition, PFOS and PFOS(4m, 5m) presented species-difference among human, Rattus norvegicus, and rainbow trout. The binding affinity with ER alpha presented an order of human >Rattus norvegicus > rainbow trout. This suggested that PFOS and PFOS(4m, 5m) have the strongest effects on human ER alpha over the other two species. As a consequence, the PFCs were more sensitive to human ER than to those of Rattus norvegicus and rainbow trout. This resulted in greater susceptibility to adverse effects, which suggested a possible underestimation of the endocrine-disrupting effects of PFCs in humans. The cross-species comparison represents the first and necessary step to identify species-specific binding mechanisms and to accurately evaluate the potential health risks of PFCs in humans.