Method for predicting effect of hydroxyl-group-substituted polybrominated diphenyl ethers on thyroid hormone and model establishing method

Abstract

The invention relates to a method for predicting the effect of hydroxyl-group-substituted polybrominated diphenyl ethers on thyroid hormone. According to the method, prediction is achieved through the following model, namely, -logREC[20]=24.22*QE[occ](-8.8eV, )+2.61*QE[vac](3.8eV, H)+0.79*logK[ow]-15.96, wherein logK[ow] represents the n-caprylic alcohol-water distribution coefficient, QE[occ](-8.8eV, O) presents energy-limited donor charges, and the number of charges accordingly supplied when hydroxyl group oxygen atoms lose 8.8eV energy is quantized. QE[vac](3.8eV, H) represents energy-limited acceptor charges and represents the value of charges accordingly accepted when hydroxyl group oxygen atoms obtain 3.8eV energy. The method has the advantages that the interference effect of 837 single-hydroxyl-group-substituted PBDEs on thyroid hormone can be rapidly predicted. The adopted molecular structure descriptor can be easily obtained, the regression analysis method is simple, and therefore experiments can be avoided when the method is used, and a large amount of labor, a large number of material resources and a large number of financial resources are saved.

Description

technical field [0001] The invention belongs to the technical field of quantitative structure-activity relationship (QSAR) for environmental ecological risk assessment, and in particular relates to the development of a method for rapidly predicting the effect of hydroxyl-substituted polybrominated diphenyl ethers (HO-PBDEs) on thyroid hormones by using the molecular structure parameters of compounds The method can be used to predict the binding ability of 837 single hydroxyl substituted HO-PBDEs to human thyroid receptors. Background technique [0002] Thyroid hormones play a very important role in the growth, development and metabolism of organisms. However, many organic compounds in the environment will interfere with thyroid hormones after they enter the organism through channels such as the food chain. Persistent toxic substances polybrominated diphenyl ethers (PBDEs) are typical thyroid hormone disruptors. In recent years, studies have shown that the thyroid hormone i...

AI Technical Summary

Problems solved by technology

However, there are only two QSAR models for the thyroid hormone interference effect of HO-PBDEs reported so far.

One is Li et al. (Li, F., Xie, Q., Li, X., Li, N., Chi, P., Chen, J., Wang, Z., Hao, C., 2010. Hormone activity of hydroxylated polybrominated diphenyl ethers on human thyroid receptor-beta:in vitro and in silico investigations.Environ.Health Perspect.118,602-606)–logREC based on 18 HO-PBDEs 20 Based on experimental measurements, a QSAR prediction model was established using 6 molecular structure descriptors including the electrophilic index (ω) that characterize the dissolution of HO-PBDEs in biological phases and the interaction with TRβ, but the descriptors used in the model The number is large, and the prediction performance is not very ideal; secondly, Li et al. (Li, X., Ye, L., Wang, X., Wang, X., Liu, H., Zhu, Y., Yu, H .,2012.Combined 3D-QSAR,molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors beta.Toxicol.Appl.Pharm.265,300-307) based on the same experimental values, using the comparative molecular similarity The 3D-QSAR model was constructed by the method of property analysis, and the interaction force field between HO-PBDEs and TRβ was clarified, but the transparency of the model is low, and it is impossible to predict a series of compounds

It can be seen that the existing QSAR models still have problems in terms of predictive ability and practical application operability.

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