Interaction\nof Per- and Polyfluoroalkyl Substances\nwith Estrogen Receptors in Rainbow Trout (Oncorhynchus\nmykiss): An <i>In Silico</i> Investigation

Fresh water sources,\nincluding lakes, such as the Great Lakes,\nare some of the most important ecosystems in the world. Despite the\nimportance of these lakes, there is increasing concern about the presence\nof per- and polyfluoroalkyl substances (PFAS)among the most\nprevalent contaminants of our timedue to the ability of PFAS\nto bioaccumulate and persist in the environment, as well as to its\nlinkages to detrimental human and animal health effects. In this study,\nPFAS exposure on rainbow trout (Oncorhynchus mykiss) is examined at the molecular level, focusing on the impact of PFAS\nbinding on the alpha (α) and beta (β) estrogen receptors\n(ERs) using molecular dynamics simulations, binding free energy calculations,\nand structural analysis. ERs are involved in fundamental physiological\nprocesses, including reproductive system development, muscle regeneration,\nand immunity. This study shows that PFAS binds to both the estrogen\nα and estrogen β receptors, albeit via different binding\nmodes, due to a modification of an amino acid in the binding site\nas a result of a reorientation of residues in the binding pocket.\nAs ER overactivation can occur through environmental toxins and pollutants,\nthis study provides insights into the influence of different types\nof PFAS on protein function.