Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Comparative Molecular Field Analysis of Dioxins and Dioxin-like Compounds

  • Ashek, Ali (Biochemicals Research Center, Korea Institute of Science and Technology) ;
  • Cho, Seung-Joo (Biochemicals Research Center, Korea Institute of Science and Technology)
  • Published : 2005.09.30
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Abstract

Because of their widespread occurrence and substantial biological activity, halogenated aromatic hydrocarbons are one of the important classes of contaminants in the environment. We have performed comparative molecular field analysis (CoMFA) on structurally diverse ligands of Ah (dioxin) receptor to explore the physico-chemical requirements for binding. All CoMFA models have given $q^{2}$ value of more than 0.5 and $r^{2}$ value of more than 0.83. The predictive ability of the models was validated by an external test set, which gave satisfactory predictive $r^{2}$ values. Best predictions were obtained with CoMFA model of combined modified training set ($q^{2}=0.631,\;r^{2}=0.900$), giving predictive residual value = 0.002 log unit for the test compound. We have suggested a model comprises of four structurally different compounds, which offers a good predictability for various ligands. Our QSAR model is consistent with all previously established QSAR models with less structurally diverse ligands. The implications of the CoMFA/QSAR model presented herein are explored with respect to quantitative hazard identification of potential toxicants.

Keywords

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