摘要
目的研究血清白蛋白(serum albumin,SA)结合松果菊苷(echinacoside,ECH)的分子作用机制。方法生理条件下,光谱法测定药物与蛋白质的结合参数,分子模拟构建ECH与牛血清白蛋白(bovine serum albumin,BSA)的结合模型,考察药物与SA结合机制。结果构建的药物与BSA结合模型表明,药物与蛋白质的相互作用力主要是氢键和范德华力,兼有疏水作用力。光谱实验表明ECH与BSA的相互作用为静态结合过程,结合强度较强,ECH与BSA分子的结合距离(r)值较小,说明发生了能量转移现象。ECH对BSA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。分析荧光相图得出ECH与BSA反应构象型态的变迁为"二态"模型。BSA与ECH相互作用的热力学参数表明ECH与BSA之间是以氢键和范德华力为主的分子间作用。荧光偏振定量证明了BSA与ECH相互作用过程中生成了非共价复合物。结论光谱实验与计算机模拟结果一致,可为研究ECH与BSA相互作用机制提供一定的参考。
Objective To explore the binding mechanism between echinacoside （ECH） and serum albumin （SA）. Methods The binding parameters were detected by spectrum experiment under physiological conditions, and the molecular modeling techniques had been used to investigate the binding mechanism between ECH and bovine serum albumin （BSA）. Results Molecular docking revealed that ECH binded to BSA mainly by hydrogen bonds and van der Waals forces, and there was a hydrophobic interaction. The results from spectroscopy indicated that the drug could bind with BSA to form static complex with significantly strong bond. The value of binding distances （r） was low, which indicated the occurrence of energy transfer. ECH affected the conformation of micro-domain and changed the hydrophobicity of the binding domain. The fluorescence phase diagram revealed that the changes on the conformational pattern of proteins had been affected by drug conformed to the ＂all-or-none＂ pattern. According to the obtained thermodynamic parameters, it also showed that the main interactional force of ECH binding with BSA was hydrogen bonds and van der Waals forces. The fluorescence polarization proved quantitatively that ECH-BSA generated a non-covalent complex. Conclusion The experimental results agree with computer molecular modeling, which provides helpful reference for the interaction mechanism of ECH binding with BSA.
出处
《中草药》
CAS
CSCD
北大核心
2014年第9期1270-1277,共8页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(20877072)
浙江省自然科学基金资助项目(Y2100458)
关键词
松果菊苷
血清白蛋白
光谱实验
分子模拟
荧光偏振定量
echinacoside
serum albumin
spectrum experiment
molecular simulation
fluorescence polarization quantitation
