Key Laboratory of Coastal Zone Environmental Processes, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai Shandong 264003, PR China.
Ecotoxicol Environ Saf. 2012 Jun;80:273-9. doi: 10.1016/j.ecoenv.2012.03.009. Epub 2012 Apr 13.
Little is known about the estrogenic activities of polycyclic aromatic hydrocarbons (PAHs) and the underlying mechanisms on estrogenic activities are still unclear. Molecular docking and quantitative structure-activity relationship (QSAR) were used to understand the relationship between molecular structural features and estrogenic activity, and to predict the binding affinity of PAHs to estrogen receptor α (ERα). From molecular docking analysis, hydrogen bonding as well as hydrophobic and π interactions were found between PAHs and ERα. Based on the docking results, appropriate molecular structural parameters were adopted to develop a QSAR model. Five descriptors were included in the QSAR model, which indicated that the estrogenic activity was related to molecular size, van der Waals volumes, shape profiles, polarizabilities and electropological states were significant parameters explaining the estrogenicity. Comparatively, the developed QSAR model had good robustness, predictive ability and mechanistic interpretability. Moreover, the applicability domain of the model was described.
关于多环芳烃（PAHs）的雌激素活性知之甚少，其雌激素活性的潜在机制仍不清楚。本研究采用分子对接和定量构效关系（QSAR）方法，以了解分子结构特征与雌激素活性之间的关系，并预测 PAHs 与雌激素受体α（ERα）的结合亲和力。从分子对接分析可知，PAHs 与 ERα 之间存在氢键以及疏水和π相互作用。基于对接结果，采用合适的分子结构参数来建立 QSAR 模型。QSAR 模型中包含 5 个描述符，表明雌激素活性与分子大小、范德华体积、形状轮廓、极化率和电拓扑状态等显著参数有关，这些参数可以解释雌激素活性。相比之下，所建立的 QSAR 模型具有良好的稳健性、预测能力和机制可解释性。此外，还描述了模型的适用域。
