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Indexed by:期刊论文

Date of Publication:2012-06-01

Journal:ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

Included Journals:SCIE、Scopus

Volume:80

Page Number:273-279

ISSN No.:0147-6513

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

Abstract: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.