Nanjing University

Qinchang Chen

Wei Shi

Hongxia Yu

Haoyue Tan

Xiaoxiang Wang

The present invention provides a model for high-throughput screening of endocrine disruptors and a method for screening the same. In the present invention, primary structural alerts, secondary structural alerts and tertiary structural alerts of compounds are extracted according to a nuclear receptor, and then the primary structural alerts, the secondary structural alerts and the tertiary structural alerts form a nuclear receptor high-throughput screening model; hierarchical structural alert matching is carried out on target compounds through the nuclear receptor high-throughput screening model, and ligand-receptor binding mode analysis and semi-quantitative prediction of binding activity and disrupting activity are performed. According to the present invention, the defect in prior art that potential nuclear receptor-mediated endocrine disruptors cannot be effectively screened in high throughput is overcome, high-throughput screening of potential nuclear receptor-mediated endocrine disruptors can be performed, and receptor competitive activity and A-Anta activity of the nuclear receptor-mediated endocrine disruptors can be determined.

Model for high-throughput screening of endocrine disruptor and method for screening same

The present patent relates to a method for qualitative identification and quantitative prediction of thyroid hormone disrupting chemicals base on the interaction between thyroid hormone receptor and co-regulators (coactivator and corepressor). The method identifies chemicals as passive antagonists, active antagonists and agonists by means of co-regulator involved molecular dynamics simulations, and predicts the relative disrupting potencies by use of binding free energy, therefore, may be used for screening of thyroid hormone disruptors among environmental pollutants. Upon more comprehensive consideration of the functioning mechanism of thyroid hormone receptor, the present invention is able to sufficiently identify thyroid hormone disruptors as agonists and antagonists, and gives more accurate prediction of the disrupting potency. Further, since nuclear receptors, just as thyroid hormone receptor, are strongly associated with co-regulators, the method may be expanded to the screening of nuclear receptor mediated endocrine disruptors.

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Jiangsu, China

Qinchang Chen