Does the oestrogen receptor encourage oestrogenicity in environmental pollutants? The case of 4-nonylphenol

Abstract

A computer-aided docking study was conducted to explore in detail the binding interactions between the structurally unlikely environmental oestrogen 4-nonylphenol (4NP) and three of its metabolites with the human oestrogen receptor alpha (hERα). Docking was done within the Schrodinger Suite 2008 using both a conventional rigid receptor with flexible ligand and the induced-fit docking protocol. Induced-fit docking allows side-chain and backbone movement in the receptor to accommodate the ligand. This study has revealed unconventional interactions between the ligands and the hERα binding pocket that could explain the observed oestrogen-like behaviour of 4NP and suggests some of the metabolites of 4NP may also be oestrogenic.

Keywords:

• docking study
• oestrogen mimic
• endocrine disruptor
• 4-nonylphenol
• induced-fit docking

Acknowledgement

This work was funded by a grant from the National Research Centre for Growth and Development, New Zealand.