基于计算模拟与光谱法研究细胞色素CYP2C9与双酚A的相互作用

基于分子对接、分子动力学模拟、紫外吸收光谱法、荧光光谱法与红外光谱法,研究了细胞色素CYP2C9与双酚A (BPA)之间的相互作用。分子对接研究表明,对接位点位于Thr364附近的空腔,结合能为-7. 51 kcal/mol;分子动力学模拟观察了10 ns内蛋白的整体构象变化,发现Thr364也是BPA与CYP2C9发生相互作用时的结合位点。光谱学研究发现CYP2C9与双酚A结合发生荧光增强现象,并且它们间的相互作用力主要为疏水作用力;二级结构中β-转角、无规则卷曲与β-折叠等也发生明显变化;随着底物浓度增加紫外吸收峰有明显上升且伴随红移。模拟计算与光谱检测均表明CYP2C9与BPA间存在较强的相互作用。

Study on the interaction between cytochrome CYP2C9 and bisphenol A based on computational simulation and spectroscopy

The interactions between CYP2 C9 and BPA was investigated by molecular docking,molecular dynamics simulation( MD),UV spectroscopy,fluorescence spectroscopy, and infrared spectroscopy,respectively. The molecular docking studies showed that the probable binding site for BPA located in the cavity near Thr364 and the binding energy was-7. 51 kcal/mol. The above conclusions were also confirmed by MD with observing the overall conformational change of the protein within 10 ns. The results of spectroscopy showed that the phenomenon of fluorescence enhancement was caused by the interaction of BPA and CYP2 C9,with the hydrophobic force as a main acting force. The content of β-sheet,random curl,β-turn,β-anti-parallel of CYP2 C9 was significant changed. With the increasing of substrate concentration,the UV absorption peak increased with red-shift obviously. Simulations and spectral experiments showed that there was strong interaction between CYP2 C9 and BPA.