分子对接模拟与多光谱法研究二水土霉素和牛血清白蛋白的相互作用

Study on the interaction between oxytetracycline dihydrate and bovine serum albumin by multi-spectral method and molecular docking simulation

在模拟生理条件下,采用荧光光谱法、三维荧光光谱法、圆二色谱法以及分子对接模拟法,研究了二水土霉素与牛血清白蛋白(BSA)之间的相互作用。荧光光谱表明,二水土霉素能有效猝灭BSA的内源荧光,猝灭机制属静态猝灭。根据Vant’s Hoff方程确定结合过程中的热力学参数ΔS、ΔH,表明两者之间作用为疏水作用力。根据Foster’s非辐射能量转移理论,计算得到结合距离r=2.56nm。同步荧光光谱、三维荧光光谱、圆二色谱结果证明盐酸四环素能够改变BSA的二级结构和微环境。分子对接模拟表明二水土霉素结合在BSA的site Ⅰ(亚域ⅡA)疏水腔中。

The interaction between oxytetracycline dihydrate and BSA were investigated with fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, circular dichroism （ CD ） and molecular docking under imitated physiological conditions. The analysis of fluorescence spectra showed that oxytetracycline dihydrate could strongly quench the fluorescence of BSA with a static quenching process. According to the Vant＇ s Hoff equation, the thermodynamic parameters AS and AH were confirmed, indicating that the predominant forces in the complex were hydrophobic force. Based on the Foister＇ s theory of non-radiation energy transfer, the specific binding distance between oxytetracycline dihydrate and BSA was determined to be 2.56 nm. The results of synchronous fluorescence, CD spectrum and three dimensional fluorescence spectrum, further demonstrated that the secondary conformation and micro-environment of BSA has been changed after the interaction with oxytetracycline dihydrate. The result of molecular docking simulation revealed that oxytetracycline dihydrate was located in sudlow＇ s site I corresponding to subdomain IIA.