MOLECULAR MODELING ANALYSIS OF PER- AND POLYFLUOROALKYL SUBSTANCES BINDING ON HUMAN FERTILIZATION PROTEINS- IZUMO1 AND EGG SURFACE JUNO

Abstract

Per- and polyfluoroalkyl substances (PFAS) have been increasingly utilized in commercial products despite growing concerns over their potential toxicological effects on human health. This study employed computational modeling to elucidate the binding interactions of PFAS with human fertilization proteins, specifically IZUMO1 and egg surface Juno targets. Molecular docking simulations revealed that out of the nineteen studied PFAS, Perfluoro?3,6?dioxaheptanoic acid (PFDHA) (-6.0 kcal/mol) and 4,8?Dioxa?3H?perfluorononanoic acid (ADONA) (-5.9 kcal/mol) exhibited high binding affinity for IZUMO1. In contrast, perfluorotridecanoic acid (PFTriA) (-7.5 kcal/mol) and 2H,2H,3H,3H?perfluorooctanoic acid 5:3 acid (5:3FTCA) (-7.0 kcal/mol) demonstrated high binding affinity for egg surface Juno. Notably, 5:3FTCA displayed high potential for simultaneous binding to both targets. Molecular dynamics simulations confirmed the high stability of PFDHA and PFTriA at their respective targets, suggesting potential disruptions to the human fertilization process. These findings imply that PFAS may pose significant reproductive toxicity, warranting further research to elucidate their mechanisms of action and develop effective countermeasures to mitigate their deleterious effects on human reproductive health.