Investigation of the Synergistic Activation of Estrogen Receptors ERα and ERβ by DIBP and MIBP: A Molecular Docking Study Based on AutoDock
Zhijian Wang · Applied and Computational Engineering · 2025
This study aims to investigate the synergistic activation effects and molecular mechanisms of diisobutyl phthalate (DIBP) and its metabolite monoisobutyl phthalate (MIBP) on estrogen receptors ERα and ERβ under combined exposure. Using AutoDock 4.2.6, molecular docking of the ligand-binding domains (LBDs) of ERα and ERβ is performed to analyze binding free energy (ΔG), key interaction sites, and spatial complementarity under single and combined treatments. The results show significant synergistic effects of DIBP and MIBP on both ERα and ERβ, which is hypothesized to result from the specific spatial complementarity of DIBP and MIBP in the receptors and the additive effect of binding energies, thereby significantly enhancing their synergistic activation of ERα and ERβ. Overall, DIBP-MIBP preferentially activate ERβ (ΔG=-9.058) more potently than ERα (ΔG=-7.73) through a two-site synergistic mechanism, suggesting that mixed exposure may enhance endocrine-disrupting effects on non-reproductive systems. This highlights the insufficient attention paid to the synergistic effects of PAEs metabolites and provides a basis for establishing receptor subtype-specific exposure limits. Given the scarcity of research on mixed exposure and the incomplete understanding of underlying mechanisms, and because molecular docking results solely reflect receptor binding capacity, the conclusions are inferred from binding energies and require validation by in vitro/in vivo experiments to demonstrate functional effects.