结合光谱法和计算模拟多角度分析2,2',4,4',5-五溴二苯醚与人血清白蛋白的作用机制

本文结合光谱法、动力学模拟(MD)和分子对接等手段,多角度地研究了2,2′,4,4′,5-五溴二苯醚(BDE-99)与人血清白蛋白(HSA)在pH=7.4模拟生理环境下的相互作用机制.首先采用MD从理论上模拟BDE-99与HSA相互作用的构象变化情况;然后利用同步荧光和三维荧光光谱法从实验角度进行验证,所得结果表明,BDE-99使HSA的疏水性增强从而导致其构象发生变化.同时,荧光光谱和紫外光谱得出BDE-99对HSA的猝灭机制属于静态猝灭和非辐射能量转移.另外,分子对接结果显示,BDE-99通过静电引力和疏水作用力结合在HSA的位点I处,这与竞争实验和热力学参数的分析结果是一致的.实验数据与模拟计算结果的相互印证,为进一步探究BDE-99和HSA的相互作用机制提供了重要的信息和参考依据.

Interaction between 2,2',4,4',5-pentabromodiphenyl ether and human serum albumin based on multi-spectroscopic and computational simulations

In this paper, the interaction mechanism between 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) and human serum albumin (HSA) in the simulated physiological environment (pH=7.4) was investigated by combing multi-spectroscopy with molecular docking and molecular dynamics simulation (MD). The results of MD reveal that the hydrophobic force plays a major role in stabilizing the HSA-BDE-99 complex, but it also affects the conformation of HSA. Furthermore, the results of synchronous fluorescence spectroscopy and three-dimensional fluorescence spectroscopy demonstrate that the microenvironment and conformation of HSA changed in the binding procedure because of the increased hydrophobicity of amino acid residues. In addition, the characterization of both fluorescence spectroscopy and ultraviolet-visible spectroscopy also implies that BDE-99 can effectively quench the intrinsic fluorescence of HSA via static quenching mechanism and non-radiative energy transfer. The distance r between BDE-99 and TRP214 is estimated to be 3.47 nm according to Förster's theory. Meanwhile, the result of the molecular docking further suggests that BDE-99 might be bound to the site I of HSA through the hydrophobic interaction and electro-static force. The thermodynamic parameters obtained from experiments are in good agreement with those based on the binding mode. Hence, it is concluded that the combination of experiment with computational simulation provides reliable information for further study of the mechanism of ligand-protein.