模拟和光谱相互验证2'-OH-BDE-28对HSA构象的影响

利用分子对接、分子动力学模拟(molecular dynamics simulation,MD)和光谱法研究2'-羟基-2,4,4'-三溴二苯醚(2'-OHBDE-28)与人血清白蛋白(HSA)的作用机制。MD模拟研究表明2'-OH-BDE-28诱导HSA的内部疏水性增强,结构松散膨胀,致使其二级结构发生改变;圆二色光谱实验与MD模拟结果相吻合,验证2'-OH-BDE-28可诱导HSA的构象变化。荧光光谱实验表明,2'-OH-BDE-28能通过静态猝灭和非辐射能量转移机制引起HSA荧光猝灭。分子对接推断2'-OH-BDE-28以氢键和疏水作用力键合在HSA的位点I处;热力学分析和竞争实验结果一致验证分子对接结果。本文将计算模拟和光谱实验相结合,从模拟和实验2个角度共同探讨2'-OH-BDE-28与HSA的作用机制,结果高度吻合。

Combined Simulation and Multispectral Investigation on the Effect of 2'-OH-BDE-28 on the Structure of HAS

In this paper, the interaction mechanism between 2''-hydroxy-2,4,4''-tribromodiphenyl ethers (2''-OH-BDE-28) and human serum albumin (HSA) was investigated by combining molecular docking, molecular dynamics simulation (MD) and multispectral techniques. The results of MD simulations indicate that the2''-OH-BDE-28-induced increase in the interior hydrophobicity of HAS occurred and the molecular structure became loose and expansive, and finally the secondary structure of HSA changed. The results of circular dichroismspectra (CD) are highly consistent with the results of MD simulations. Moreover, the results of fluorescence spectroscopy experiment also show that the intrinsic fluorescence of HSA was quenched by 2''-OH-BDE-28 through static quenching and non-radiation energy transfer. Molecular docking results indicate that 2''-OH-BDE-28 coordinated with the site I of HAS through hydrophobic forces and hydrogen bonds. Hence, a similar conclusion was obtained from the thermodynamics parameters and competitive experiment to verify the results from molecular docking. Excellent agreement was obtained between computer simulations and multispectral experiments to study the mechanism on the interaction between 2''-hydroxy-2,4,4''- tribromodiphenyl ethers and human serum albumin.