光谱法结合分子模拟分析乳铁蛋白与药物恩诺沙星的互作分子机理

Interaction Characteristics of Enrofloxacin Binding with Bovine Lactoferrin Using Spectroscopy and Molecular Modeling

利用光谱实验结合计算机模拟技术研究了药物恩诺沙星(Enrofloxacin,EFLX)与牛乳铁蛋白(Bovine lactoferrin,BLF)的相互作用机理。测定反应体系的结合参数、能量转移参数及热力学函数,考察EFLX对BLF分子构象的影响,并模拟EFLX-BLF结合反应的分子模型。结果表明,药物分子与牛乳铁蛋白的相互作用表现为动态结合过程,结合强度适中,EFLX与BLF分子的结合距离r值较小,说明发生了能量转移现象。EFLX影响BLF的结构域微区构象,降低结合位域的疏水性。荧光相图技术解析出EFLX与BLF反应构象型态的变迁为"二态模型"。EFLX-BLF的热力学参数表明两者间是以氢键和范德华力为主的分子间作用。分子建模结果显示,EFLX与BLF的相互作用主要为氢键和范德华力,兼有疏水作用力。计算机分子模拟与实验测试获得了一致性结果。

A combination of spectral experiment and molecular modeling techniques was used to characterize the binding mechanism between enrofloxacin（EFLX）and bovine lactoferrin（BLF）.The binding constants,energy transfer paremeters and thermodynamic parameters were investigated.The influence of EFLX on molecular conformation of BLF and the molecular models of EFLX-BLF were observed and established.The results showed that dynamic quenching exited between EFLX and BLF with moderate bond.The value of binding distances（r） was low,indicating the occurrence of energy transfer.The drug had conformation effect on BLF,which resulted in the decrease of hydrophobic environment of the binding domain in BLF.According to the obtained thermodynamic parameters,the main interaction forces between EFLX and BLF were hydrogen bonds and Van der Waals forces.The results of molecular modeling revealed that hydrogen bonds and Van der Waals forces are the main binding forces in the EFLX-BLF system,combining with hydrophobic interactions.Molecular modeling was agreed in the experiment results,which provided helpful reference for the study of molecular reaction mechanism of the quinolones binding with bovine lactoferrin.