基于分子对接和电子舌感官分析的罗汉果甜苷单体与甜/苦味受体构效关系研究  

Conformational Relationship between Mogroside Monomers and Sweet/Bitter Taste Receptors Based on Molecular Docking and Electronic Tongue Sensory Analysis

作　　者：陈靓 唐国玮 朱康明 龙斌 田星[1,4] CHEN Liang;TANG Guowei;ZHU Kangming;LONG Bin;TIAN Xing(School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;School of Food Science and Bioengineering,Changsha University of Science and Technology,Changsha 410114,China;School of Informatics,Hunan University of Chinese Medicine,Changsha 410208,China;TCM and Ethnomedicine Innovation&Development International Laboratory,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学药学院,湖南长沙410208 [2]长沙理工大学食品与生物工程学院,湖南长沙410114 [3]湖南中医药大学信息科学与工程学院,湖南长沙410208 [4]湖南中医药大学,湖南省中医药民族医药国际联合实验室,湖南长沙410208

出　　处：《食品工业科技》2024年第24期107-117,共11页Science and Technology of Food Industry

基　　金：湖南省自然科学基金面上科学基金项目(2023JJ30445);湖南省教育厅优秀青年项目(22B0378);湖南省中医药大学“双一流”建设学科“揭榜挂帅”项目(22JBZ053);湖南省中医药管理局科研项目(B2024012)。

摘　　要：目的:从分子水平上揭示罗汉果甜苷单体与人类味觉受体之间的相互作用机制。方法:利用I-TASSER Server建立甜味受体(hT1R2、hT1R3)和苦味受体(hT2R4、hT2R14)的同源模型,依据ERRAT值、拉氏图、C-score等指标评估模型质量,选择最高质量的模型,通过AutoDock Vina模拟软件与Mogroside III、Mogroside IV、Mogroside V和Siamenoside I四种已知甜度罗汉果甜苷进行分子对接;构建罗汉果甜苷甜/苦味预测模型并对未知甜度罗汉果甜苷的甜/苦味进行预测;在此基础上,运用电子舌智能分析不同罗汉果甜苷单体的甜/苦味特征值,探究不同结构罗汉果甜苷单体与甜/苦味关键属性间的关系。结果:分析受体-配体相互作用关系发现R1位置葡萄糖基团数目增多可以使罗汉果甜苷苦味降低,R2位置葡萄糖基团数目增多可以增强甜度,减弱苦味。甜味受体结合位点空间较大,有利于罗汉果甜苷进入,而苦味受体结合位点空间较小,限制配体进入。而电子舌所测定的甜/苦味特征值与分子对接得到的结合自由能高度一致,验证了预测结果的准确和可靠性。此外,研究还发现甜/苦味比例在开发特定口感甜味剂中具有重要意义,并成功预测了未知风味的罗汉果甜苷甜/苦味。结论:罗汉果甜苷的甜度与其葡萄糖基团的数量具有一定相关性。研究结果不仅为罗汉果天然甜味剂的研发提供了重要的理论支撑,同时也为新型天然甜味剂的筛选和开发提供了科学基础和理论支持。Objective:To reveal the interaction mechanism between mogroside monomers and human taste receptors at molecular level.Methods:The homologous models of sweet taste receptors(hT1R2,hT1R3)and bitter taste receptors(hT2R4,hT2R14)were established by I-TASSER Server.Model quality was evaluated according to ERRAT value,ramachandran plot,C-score and the model with the highest quality was selected.Molecular docking with MogrosideⅢ,MogrosideⅣ,Mogroside V and Siamenoside I were performed by AutoDock Vina simulation software.The sweet/bitter taste prediction model of mogroside was constructed and the sweet/bitter taste of mogroside with unknown sweetness were predicted.On the basis of this,the electronic tongue system intelligence was used to analyze the sweet/bitter characteristic values of different structures of mogroside monomers and to explore the relationship between different structures of mogroside monomers and the key attributes of sweet/bitter taste.Results:The analysis of receptor-ligand interaction showed that increasing the number of glucose groups at R1 position could reduce the bitterness of mogroside,and increasing the number of glucose groups at R2 position could enhance the sweetness and weaken the bitterness.The binding site space of sweet taste receptors was large,which was conducive to the entry of mogroside,while the binding site space of bitter taste receptors was small,which limited the entry of ligands.The sweet/bitter characteristic values measured by the electronic tongue were in high agreement with the binding free energy obtained by molecular docking,which verified the accuracy and reliability of the predicted results.In addition,the study also revealed the importance of sweet/bitter ratios in the development of taste-specific sweeteners and successfully predicted the sweet/bitter taste of mogroside sweeteners of unknown flavor.Conclusion:The sweetness of mogroside had a certain correlation with the number of glucose groups.The research results not only provide important theoretical support f

关 键 词：同源建模 分子对接 甜/苦味受体 交互作用 电子舌 罗汉果甜苷 

分 类 号：R932[医药卫生—生药学]