Investigating mechanism of sweetness intensity differences through dynamic analysis of sweetener-T1R2-membrane systems

Yulu Miao; Hui Ni; Xingyi Zhang; Fengdong Zhi; Xiang Long; Xuepeng Yang; Xiao He; Lujia Zhang

doi:10.1016/j.foodchem.2021.131807

Investigating mechanism of sweetness intensity differences through dynamic analysis of sweetener-T1R2-membrane systems

Food Chem. 2022 Apr 16:374:131807. doi: 10.1016/j.foodchem.2021.131807. Epub 2021 Dec 7.

Authors

Yulu Miao¹, Hui Ni², Xingyi Zhang², Fengdong Zhi¹, Xiang Long², Xuepeng Yang³, Xiao He⁴, Lujia Zhang⁵

Affiliations

¹ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
² College of Food and Biological Engineering, Jimei University, Xiamen 361021, China.
³ School of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, China.
⁴ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China. Electronic address: xiaohe@phy.ecnu.edu.cn.
⁵ Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China; NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China. Electronic address: Ljzhang@chem.ecnu.edu.cn.

PMID: 34915374
DOI: 10.1016/j.foodchem.2021.131807

Abstract

Knowing the mechanism of action of sweet taste receptors is important for the design of new, healthy sweeteners. However, little is known about the structures and recognition mechanisms of these receptors. 28 sweeteners were assessed by molecular docking, and 8 typical sweeteners were chosen to construct sweetener-T1R2-membrane systems to analyze interactions between receptor and sweeteners. Natural sweeteners with low-intensity sweetness, such as fructose and xylitol, were released from the Venus flytrap domain at ∼30 ns, with displacements greater than 50 Å. In contrast, artificial neotame and advantame bound stably to the receptor, within 5 Å. Van der Waals interactions were significant in high-intensity sweetener systems, imparting an energy difference of over 15 kcal/mol between neotame (artificial sweetener) and fructose (natural). These results provide a deeper understanding of the mechanisms of sweetener function and offer a new direction for the design of sweeteners.

Keywords: Molecular dynamics simulation; Sweetener intensity; Sweetener–T1R2–membrane system; Venus flytrap domain opening.

MeSH terms

Excipients
Molecular Docking Simulation
Receptors, G-Protein-Coupled
Sweetening Agents*
Taste*

Substances

Excipients
Receptors, G-Protein-Coupled
Sweetening Agents