Screening methods for thyroid hormone disruptors based on co-regulator involved simulations

摘要

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.