Docking and QSAR study on the binding interactions between polycyclic aromatic hydrocarbons and estrogen receptor

Area of Science:

• Environmental Chemistry
• Toxicology
• Computational Chemistry

Background:

• Estrogenic activities of polycyclic aromatic hydrocarbons (PAHs) are poorly understood.
• Mechanisms underlying PAH estrogenicity remain unclear.

Purpose of the Study:

• To investigate the estrogenic activities of PAHs.
• To elucidate the mechanisms of PAH interaction with estrogen receptor alpha (ERα).
• To develop a quantitative structure-activity relationship (QSAR) model for predicting PAH binding affinity to ERα.

Main Methods:

• Molecular docking simulations were employed to analyze interactions between PAHs and ERα.
• Quantitative structure-activity relationship (QSAR) modeling was developed based on docking results.
• Key molecular descriptors influencing estrogenic activity were identified.

Main Results:

• Molecular docking revealed hydrogen bonding, hydrophobic, and π interactions between PAHs and ERα.
• A QSAR model incorporating five descriptors (molecular size, van der Waals volumes, shape, polarizability, electropological states) was established.
• These descriptors significantly explain the observed estrogenicity of PAHs.

Conclusions:

• The developed QSAR model demonstrates good robustness, predictive capability, and mechanistic interpretability.
• The model provides insights into the structural determinants of PAH estrogenicity.
• The study enhances understanding of environmental estrogens and their interactions with the estrogen receptor.