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论文类型：期刊论文

发表时间：2012-06-01

发表刊物：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

收录刊物：SCIE、Scopus

卷号：80

页面范围：273-279

ISSN号：0147-6513

关键字：Polycyclic aromatic hydrocarbons (PAHs); Estrogenic activity; Molecular docking; Quantitative structure-activity relationship (QSAR); Applicability domain

摘要：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 alpha (ER alpha). From molecular docking analysis, hydrogen bonding as well as hydrophobic and pi interactions were found between PAHs and ER alpha. 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. (C) 2012 Elsevier Inc.. All rights reserved.