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Ecotoxicol Environ Saf. 2013 Mar;89:143-9. doi: 10.1016/j.ecoenv.2012.11.020. Epub 2012 Dec 20.

Docking and CoMSIA studies on steroids and non-steroidal chemicals as androgen receptor ligands.

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State Key Laboratory of Pollution Control and Resources Reuse, School of the Environment, Nanjing University, Nanjing 210046, People's Republic of China.


While some synthetic chemicals have been demonstrated to disrupt normal endocrine function by binding to the androgen receptor (AR), the mechanism by which ligands bind to the ligand binding domain (LBD) remained unclear. In this study, docking and comparative molecular similarity index analysis (CoMSIA) were performed to study the AR ligand binding mechanism of steroids and non-steroidal chemicals. The obtained docking conformations and predictive CoMSIA models (r(pred)(2)values as 0.842 and 0.554) indicated the primary interaction site and key residues in the binding process. The major factors influence the binding affinity of steroids and non-steroidal chemicals were electrostatic and hydrophobic interactions, respectively. The results indicated that besides amino-acid residues Gln711, Arg752 and Thr877 which have previously been reported to be important in binding ligands, Leu701 and Leu704 are also important. Residues Val746, Met749 and Phe764 are crucial only for steroids, while Met742 and Met787 are important only for non-steroidal chemicals. This knowledge of key interactions and important amino-acid residues governing ligands to the AR allow better prediction of potency of AR agonists so that their potential to disrupt AR-mediated pathways and to design less potent alternatives.

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