Molecular docking and dynamics reveal strong binding of BPA substitutes (BPS, BPF) to human estrogen receptor alpha: implications for endocrine disruption

Abstract

There is currently little information on the effects of bisphenol S (BPS) and bisphenol F (BPF), two alternatives to bisphenol A (BPA), on human endocrine systems; most research on these compounds is conducted on animal models. This study examines how BPA, BPS, and BPF bind to the human estrogen receptor alpha using molecular docking and dynamics, as well as the potential endocrine disruption caused by these substances in people. This research uses AutoDock Tools and AutoDock Vina to predict the binding locations of BPS and BPF inside the estrogen receptors ligand-binding domain (LBD). Gromacs 2021 molecular dynamics simulations were run for 200 ns in order to determine the binding free energies of BPA, BPS, and BPF as well as to evaluate the stability of docking data. Results indicate that BPS and BPF, similarly to BPA, bind stably to the estrogen receptor through hydrogen bonding and hydrophobic interactions, indicating potential endocrine-disrupting effects. BPF exhibited the strongest binding affinity, primarily due to significant hydrophobic interactions involving residues like LEU346 and LEU384. BPA and BPF formed stable hydrogen bonds, whereas BPS displayed slightly lower stability and more varied interactions. Throughout the simulations, all ligands consistently occupied the receptors active site, highlighting persistent binding. These findings imply that BPS and BPF may pose comparable health risks to BPA, though their unique interaction patterns suggest different underlying mechanisms. Experimental validation in human systems is critical to corroborate these computational predictions and evaluate the safety of BPA substitutes.