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.