QSAR models for binding of estrogenic compounds to estrogen receptor alpha and beta subtypes.

We have developed Quantitative Structure-Activity Relationship (QSAR) models based on Comparative Molecular Field Analysis (CoMFA) for 31 estrogenic chemicals whose relative binding affinity (RBA) is available for both ER-alpha and ER-beta. The models demonstrated a significant correlation (r2>0.95) between the CoMFA-calculated steric/electrostatic fields and corresponding RBA data and a good predictive capability (q2>0.6) based on cross-validation. The CoMFA models and contour plots obtained for ER-alpha and ER-beta suggest a close similarity between the receptors in terms of mode of binding and provide a rational basis for ligand selectivity.