多光谱法结合分子模拟分析洛索洛芬和金属离子影响三磷酸腺苷对蛋白的作用机制

Multi-Spectroscopy Combined with Molecular Docking to Analyze the Effect of Loxoprofen and Metal Ions on the Mechanism of Adenosine Triphosphate to Protein

利用光谱法结合分子模拟分析探究在血浆中常见的5种金属元素存在下,洛索洛芬对三磷酸腺苷抑制血清白蛋白的影响。研究结果表明,在洛索洛芬钠的影响下,三磷酸腺苷以静态猝灭的模式抑制蛋白的荧光强度。ΔG<0,ΔH<0且ΔS>0,表明两种药物与蛋白的结合为自发的放热反应,作用力以氢键和范德华力为主。通过希尔方程,测定出希尔系数均略大于1,表明洛索洛芬和三磷酸腺苷之间有弱的正协同效应;同步荧光数据说明结合位点更加接近于酪氨酸残基。添加的镁、钴和锰明显增强抑制作用,反而铬和铁削弱了抑制作用。分子对接法证明光谱实验的结论,为后续进一步开展探究临床实践过程中应用合并用药对疾病进行治疗奠定一定的理论基础。

The effects of loxoprofen on inhibition of serum albumin by adenosine triphosphate in the presence of five common metal elements in plasma were investigated by spectrometric method combined with molecular simulation.The results showed that under the influence of loxoprofen,adenosine triphosphate inhibited the fluorescence of proteins in a static quenching mode.ΔG<0,ΔH<0 andΔS>0 showed the interaction was spontaneous exothermic reaction and mainly driven by Vander Waals forces and hydrogen.The values of Hill′s coefficients obtained by Hill equation were slightly bigger than 1,which concluded that there was weak positive cooperative effect between loxoprofen and adenosine triphosphate.The synchronous fluorescence data illustrated that the binding site was close to tyrosine residue.The addition of magnesium,cobalt and manganese only significantly enhanced the inhibition,but also weakened by chromium and iron.The physical modeling method is used to further illustrate the conclusions from spectroscopic experiment.In this study,spectrometric analysis and molecular docking simulation were combined to validate the prediction of interaction of the two drugs on serum albumin without performing cell experiments.Molecular docking method proved the conclusion of spectrograph experiment.It provides theoretical basis for exploration of the application of combination drugs for treating diseases in clinical practice.