转铁蛋白转运培氟沙星的分子作用机制研究

Molecular transport mechanism of pefloxacin mesylate binding with transferrin

利用光谱实验结合计算机模拟技术研究转铁蛋白(Transferrin,Tf)转运药物培氟沙星(pefloxacinmesylate,PM)的相互作用机制,测定反应体系的结合参数及热力学函数,考察PM对Tf分子构象的影响,并讨论结合反应的分子作用机制。结果表明,药物分子与转铁蛋白的相互作用表现为动态结合过程,PM与Tf分子的结合距离r值较小,说明发生了能量转移现象。药物分子对转铁蛋白分子的结构域微区构象产生影响,使结合位域的疏水性发生改变。转铁蛋白转运培氟沙星的热力学参数表明PM与Tf之间是以疏水作用力为主的分子间作用机制。依据计算机模拟建立的分子对接结果显示,PM与Tf的相互作用主要为疏水作用,兼有氢键的存在,计算机分子模拟与光谱实验结果一致。

The binding mechanism between pefloxacin mesylate （PM） and transferrin （Tf） was explored using spectral experiment combined with molecular modeling techniques. The binding parameters and thermodynamic functions of PM-Tf solution system were measured at different temperatures. The effect of PM on molecular conformation of Tf was investigated and the interaction mechanism was also discussed. The results showed that dynamic quenching mechanism occurs with PM binding to Tf. The value of binding distances （r） is low, which indicates the occurrence of energy transfer. The drug had conformational effect on Tf, which resulted in changes of hydrophobic environment of the binding domain in Tf. According to the obtained thermodynamic parameters, the main interaction force between PM and Tf is attributed to hydrophobic bonding. The results of molecular modeling revealed that hydrophobic and hydrogen bonds are main binding forces in the PM-Tf system. These results were in accordance with spectral experiments. The research results have given a better theoretical reference for the study of pharmacological mechanism between protein and quinolone.