Molecular dynamics data

Stevioside and rebaudioside-A are high-intensity natural sweeteners which are popularly used in foods and beverages. However, their structure-activity relationships (SARs), especially the sweetness determinant sites (glucophores) of these sweeteners remain elusive. In this research, we firstly modeled the human sweet taste receptor Tas1R2/Tas1R3,and then docked the twosweet molecules into the receptor, respectively. Subsequently, functional mutagenesis analysis of potential residues located in the binding pocket of human Tas1R2 were carriedoutby the cell-based calcium mobilization assay. Based on these findings, we identified the crucial glucophores of stevioside and rebaudioside-A interacting with the receptor residues and determining the sweetness of the two sweetenersas well as their stereochemical arrangements. Moreover, molecular dynamics analysis was performedto elucidate the atomic mechanism of receptor activation by stevioside. Compared with previous findings, our results provide a novel and deeper insight into the SARs of stevioside and rebaudioside-A, which are meaningful guidelines for further potentialstructural modification and improvement of their sweetening properties.

甜菊苷（Stevioside）与莱鲍迪苷A（rebaudioside-A）是一类高强度天然甜味剂，广泛应用于食品与饮料领域。然而，二者的构效关系（structure-activity relationships, SARs），尤其是这类甜味剂的甜味决定位点（生甜团，glucophores）仍有待阐明。本研究首先构建了人类甜味受体Tas1R2/Tas1R3的三维模型，随后将两种甜味分子分别对接至该受体。随后，针对人类Tas1R2结合口袋内的潜在残基，通过基于细胞的钙动员检测（cell-based calcium mobilization assay）开展了功能诱变分析。基于上述实验结果，本研究明确了甜菊苷与莱鲍迪苷A中，与受体残基相互作用、决定二者甜味特性的关键生甜团，以及其立体化学排布方式。此外，本研究还通过分子动力学分析，阐明了甜菊苷激活该受体的原子层面作用机制。与既往研究成果相比，本研究结果为甜菊苷与莱鲍迪苷A的构效关系提供了全新且更深入的认知，可为后续开展结构修饰以优化其甜味性能提供具有指导意义的参考依据。