QSAR prediction of antagonistic activity of PCBs towards human PXR by using heuristic method and best subset modeling

Polychlorinated biphenyls(PCBs) can antagonize human pregnane X receptor(hPXR) activation.Such chemicals could pose a serious threat to the reproductive and developmental ability of humans.The quantitative structure activity relationship(QSAR) provides a promising method for the estimation of PCBs’ antagonistic activity.In this investigation,a QSAR model was developed by using heuristic method and best subset modeling(r2 = 0.873,q2LOO=0.742).The built model was validated externally by splitting the original data set into training and prediction sets.The results of the model derived are as follows:r2 = 0.907,q2LOO=0.709,r2pred=0.676,suggesting developed QSAR model had good robustness and predictive ability.The applicability domain(AD) of the model was assessed by Williams plot.The antagonistic activity(?logKi) of 108 PCBs,which are unavailable by experiment at present,was predicted within the applicability domain of the model.The critical structural features related to the activity of PCBs were identified.     

3D-QSAR and docking studies of estrogen compounds based on estrogen receptor β

Close attention has been paid to estrogen compounds because these chemicals may pose a serious threat to the health of humans and wildlife. Estrogen receptor (ER) exists as two subtypes, ERα and ERβ. The difference in amino acids sequence of the binding sites of ERα and ERβ might lead to a result that some synthetic estrogens and naturally occurring steroidal ligands have different relative affinities and binding modes for ERα and ERβ. In this investigation, comparative molecular similarity indices analysis...