基于分子对接和表面等离子共振技术分析虾青素与跨膜转运蛋白CD36的结合作用  

Analysis of Astaxanthin Binding to Transmembrane Transporter Protein Cluster Determinant 36 Using Molecular Docking and Surface Plasmon Resonance

作　　者：张俊林 陈祉晴 郑钦生 肖杰 曹庸[1] 刘晓娟[1] ZHANG Junlin;CHEN Zhiqing;ZHENG Qinsheng;XIAO Jie;CAO Yong;LIU Xiaojuan(Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods,College of Food Science,South China Agricultural University,Guangzhou 510642,China)

机构地区：[1]华南农业大学食品学院,广东省功能食品活性物重点实验室,广东广州510642

出　　处：《食品科学》2023年第12期102-107,共6页Food Science

基　　金：国家自然科学基金面上项目(32172195);广东省自然科学基金项目(2019A1515011391,2021A1515012158);广州市重点研发计划项目(SL2022B03J00806)。

摘　　要：目的:探究虾青素与跨膜转运蛋白白细胞分化抗原36(cluster determinant 36,CD36)的结合作用。方法:采用分子对接技术模拟虾青素与CD36的结合作用,结合算法获得相互作用参数,确定结合位点,建立最佳匹配模型。同时,利用表面等离子共振技术测定分子间相互作用的结合和解离常数。结果:虾青素进入CD36内部的疏水腔中,对接结合能为-11.70 kcal/mol,且呈剂量依赖性结合,解离平衡常数KD为1.00×10^(-6) mol/L,表明虾青素与CD36以高亲和力结合,且动力学曲线显示虾青素与CD36的结合模式为慢结合慢解离;虾青素与CD36更多的氨基酸结合形成疏水相互作用,不同于叶黄素和β-胡萝卜素与CD36的极性氨基酸Asn53形成弱的范德华力,虾青素与天冬酰胺Asn53形成氢键作用,可能是虾青素以高亲和力结合CD36的部分原因,同时推断虾青素末端环上的酮基或羟基与酮基形成的α-羟基酮对于形成氢键起一定作用。结论:虾青素与CD36发生自发的相互作用且以高亲和力结合,结合模式为慢结合慢解离,从而实现有效的跨膜转运。Purpose:To investigate the binding interaction of astaxanthin with the transmembrane transporter protein cluster determinant 36(CD36).Methods:Molecular docking was used to simulate the binding interaction between astaxanthin and CD36,the interaction parameters were obtained using an algorithm,the number of binding sites was determined,and the best matching model was established.Moreover,surface plasmon resonance(SPR)was used to measure the binding and dissociation constants of intermolecular interactions.Results:Astaxanthin entered the hydrophobic cavity inside CD36,and the docking binding energy was−11.70 kcal/mol,suggesting a dose-dependent effect.Besides,the equilibrium dissociation constant KD was 1.00×10^(-6) mol/L,indicating that astaxanthin bound to CD36 with high affinity,and the kinetic curves showed that the binding mode of astaxanthin and CD36 was slow binding and slow dissociation.Astaxanthin bound to more amino acids of CD36 through hydrophobic interaction.Unlike lutein andβ-carotene,which formed weak van der Waals force with the polar amino acid Asn53 of CD36,astaxanthin formed hydrogen bonding with Asn53,which may be partly responsible for the high-affinity binding between astaxanthin and CD36.Furthermore,it was inferred that the ketone group on the terminal ring of astaxanthin orα-hydroxy ketone formed by hydroxyl and ketone groups played a certain role in the formation of hydrogen bonds.Conclusion:Astaxanthin interacts spontaneously with CD36 with high affinity,and the binding mode is slow binding and slow dissociation,contributing to efficient transmembrane transport.

关 键 词：虾青素 白细胞分化抗原36 分子对接 表面等离子共振技术 

分 类 号：TS201.2[轻工技术与工程—食品科学]