中文摘要：

甲状腺素（thyroid hormones,THs）干扰物（thyroid disrupting chemicals,TDCs）能与THs竞争甲状腺素转运蛋白（transthyretin,TTR）的结合位点而影响THs体内平衡.TDCs结构中的卤素基团是影响TDCs与TTR相互作用的关键性结构因子.本研究分析了卤代化合物与TTR的复合物结构和卤代化合物与TTR的相互作用势（logRP）,发现卤键和卤氢键、诱导效应和疏水效应是影响有机卤化合物与TTR相互作用的关键因素.卤键（主要是卤氧键）和卤氢键的形成,增强了有机卤化合物与TTR的相互作用.对可电离化合物,诱导效应是卤素基团影响logRP大小的重要因素,疏水效应是卤素基团影响多溴联苯醚（PBDEs）等不可电离化合物与TTR相互作用的主要因素.

英文摘要：

Thyroid disrupting chemicals（TDCs） can compete for the binding sites of transport proteins with thyroid hormones（THs） and alter the homeostasis of THs. The halogen moieties in TDCs play key role in determining the interactions between TDCs and transthyretin（TTR）. Herein, the effects of halogenation on the binding interaction was investigated by analyzing the TTR crystal structures, the TDCs-TTR complex from molecular simulation, and the relative competing potency of a chemical with T4 binding to hTTR（logRP）. We found that the halogen moieties in TDCs can affect the binding interactions by forming halogen bonds and halogen-hydrogen bonds with TTR and through inductive effects and hydrophobic effects. The halogen bonds（mainly halogen-oxygen bonds） and halogen-hydrogen bonds enhance the binding between organic halogenated compounds and TTR. Besides, for the halogenated phenolic compounds, the inductive effect is a main factor determining the logRP values. The hydrophobic effect is a critical factor governing the interactions between non-ionizable compounds（e.g. polybrominated diphenyl ethers） and TTR.