典型持久性有机污染物与抑癌基因相互作用的分子模拟与验证

Abstract

Synthetic organic chemical pollutants are a serious problem to human welfare and the environment. Ecological risk assessment of synthetic organic compounds offers a precautionary approach that assesses the potential danger of these pollutants. The development of a computational toxicology model based on the mechanism should be able to predict the risks of chemicals efficiently and prioritize pollutants. Molecular simulations and spectroscopic techniques were used to study the interaction between 2,2,4,4-tetra-bromodiphenyl ether (BDE-47) and the promoter region segment of the p53 gene (p53-DNA). The spectroscopic methods included ultraviolet-visible absorption spectrophotometry, fluorescence spectroscopy using ethidium bromide (EB) as the fluorescent probe, and measurement of the melting point. As revealed by molecular docking, BDE-47 intercalated partially with p53-DNA, and π-π and groove binding interactions between BDE-47 and p53-DNA were observed. Spectroscopic results showed that as the concentration of BDE-47 increased, p53-DNA produced a hyperchromic effect and the fluorescence system of EB-p53-DNA had a static quenching effect. This suggests that the binding mode of BDE-47 with p53-DNA involved partial intercalation accompanied by groove binding interactions. Thus, the spectroscopic results are congruent with the molecular simulations. The binding constant was calculated to be 7.24×103 L/mol. The mechanism of the interaction between BDE-47 and p53-DNA was elucidated at atomic resolution, which provides the molecular basis for risk screening and management of chemicals.