Ligand-based identification of environmental estrogens
- Environmental Protection Agency, Research Triangle Park, NC (United States)
- Los Alamos National Lab., NM (United States)
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); and others
Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to examine the estrogen receptor (ER) binding affinities of a series of structurally diverse natural, synthetic, and environmental chemicals of interest. The CoMFA/3D-QSAR model is statistically robust and internally consistent, and successfully illustrates that the overall steric and electrostatic properties of structurally diverse ligands for the estrogen receptor are both necessary and sufficient to describe the binding affinity. The ability of the model to accurately predict the ER binding affinity of an external test set of molecules suggests that structure-based 3D-QSAR models may be used to supplement the process of endocrine disrupter identification through prioritization of novel compounds for bioassay. The general application of this 3D-QSAR model within a toxicological framework is, at present, limited only by the quantity and quality of biological data for relevant biomarkers of toxicity and hormonal responsiveness. 28 refs., 12 figs., 9 tabs.
- OSTI ID:
- 589091
- Journal Information:
- Chemical Research in Toxicology, Journal Name: Chemical Research in Toxicology Journal Issue: 8 Vol. 9; ISSN 0893-228X; ISSN CRTOEC
- Country of Publication:
- United States
- Language:
- English
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