多溴联苯醚与人血清白蛋白相互作用的表面等离子体共振及分子对接

采用表面等离子体共振(SPR)技术, 在模拟生理条件下实时动态研究了8种典型多溴联苯醚(PBDEs)与人血清白蛋白(HSA)相互作用的动力学和热力学行为. 通过分子对接模拟研究了PBDEs与HSA相互作用的分子机制, 探讨了不同PBDEs与蛋白的结合模式及作用力. 动力学实验结果表明, PBDEs中溴原子的个数和取代位置对相互作用有规律性的影响. 溴原子通过改变PBDEs分子与HSA作用过程中的解离速率来影响其亲和力, 溴原子个数越多, PBDEs与HSA作用的亲和力越强; 而取代基位置则影响PBDEs与HSA作用结合速率的快慢, 同分异构体中间位取代溴的亲和力大于邻位取代溴. 分子对接结果显示, 8种PBDEs主要结合于HSA的Site I位点, 但结合位点周边氨基酸残基类型的差异影响了结合力. 范德华力和氢键对结合能的贡献远大于静电力.

Interactions Between Polybrominated Diphenyl Ethers and Human Serum Albumin Using SPR and Molecular Docking

The interactions between eight polybrominated diphenyl ethers(PBDEs) and human serum albumin(HSA) were studied by using surface plasmon resonance(SPR) and molecular docking technologies. The results of SPR kinetic analysis showed that both the number and substitution position of bromine on PBDEs had regular influences on the interaction. Bromine atoms mainly affected the dissociation rate of interaction, cau- sing the affinity of PBDE and HSA to increase with the number of bromine atoms. The position of bromine on PBDEs mainly affected the association rate of interaction, resulting in the high affinity of m-substituted PBDE and HSA than that of o-substituted PBDE in isomers. The results of molecular docking indicated although all PBDEs were mainly bound to site I of HSA, the difference of amino acid residues around the binding site affected the binding ability. The van der Waals force and hydrogen bond force had greater contribution to binding free energy than electrostatic force. The experimental datum of SPR were in good agreement with the results of computer simulation.