Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors

Umami is a fundamental taste sensation, often described as a delicious and pleasant flavor perception. To enhance or complement the original flavor and meet the tastes of diverse regions, umami dipeptides have been extensively utilized in global food manufacturing. Currently, the application and pur...

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Main Authors: Kaixuan Hu, Guangzhou Sun, Wentong Yu, Mengyu Zhang, Shuang Wang, Yujie Cao, Dongling Hu, Li Liang, Gang He, Jianping Hu, Wei Liu
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/13/2774
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author Kaixuan Hu
Guangzhou Sun
Wentong Yu
Mengyu Zhang
Shuang Wang
Yujie Cao
Dongling Hu
Li Liang
Gang He
Jianping Hu
Wei Liu
author_facet Kaixuan Hu
Guangzhou Sun
Wentong Yu
Mengyu Zhang
Shuang Wang
Yujie Cao
Dongling Hu
Li Liang
Gang He
Jianping Hu
Wei Liu
author_sort Kaixuan Hu
collection DOAJ
description Umami is a fundamental taste sensation, often described as a delicious and pleasant flavor perception. To enhance or complement the original flavor and meet the tastes of diverse regions, umami dipeptides have been extensively utilized in global food manufacturing. Currently, the application and purification techniques of dipeptides are relatively mature, while their umami mechanisms and molecular modification are both scarce. In this work, the 3D structure of the umami dipeptide target T1R1/T1R3 was first obtained through sequence alignment and homology modeling, then followed by the successful construction of a database containing 400 samples of dipeptides. Subsequently, the complex models of T1R1/T1R3, respectively, with DG (Asp-Gly) and EK (Glu-Lys) (i.e., T1R1_DG/T1R3, T1R1/T1R3_DG, T1R1_EK/T1R3, and T1R1/T1R3_EK) were obtained via molecular docking and virtual screening. Finally, based on comparative molecular dynamics (MD) simulation trajectories, the binding free energy was calculated to investigate receptor–ligand recognition and conformational changes, providing some implications for potential modifications of umami dipeptides. T1R1 tends to bind relatively small umami dipeptides, whereas T1R3 does the opposite, both of which favor the recognition of acidic and hydrophilic dipeptides. By comparing strategies such as hydroxyl introduction and chain length alteration, electrostatic effects may be more important than non-polar effects in molecular design. This work not only explores the recognition mechanism of umami dipeptides with the receptor T1R1/T1R3 showing certain theoretical significance, but also provides feasible suggestions for dipeptide screening and modification having certain application value.
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spelling doaj-art-890ca8a718ec4a9c839ee9093cbebc2a2025-08-20T03:16:42ZengMDPI AGMolecules1420-30492025-06-013013277410.3390/molecules30132774Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 ReceptorsKaixuan Hu0Guangzhou Sun1Wentong Yu2Mengyu Zhang3Shuang Wang4Yujie Cao5Dongling Hu6Li Liang7Gang He8Jianping Hu9Wei Liu10Bamboo & Forest Institute of Science, Technology and Industrial Innovation, Leshan Normal University, Leshan 614004, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaKey Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, School of Pharmacy, Chengdu University, Chengdu 610106, ChinaBamboo & Forest Institute of Science, Technology and Industrial Innovation, Leshan Normal University, Leshan 614004, ChinaUmami is a fundamental taste sensation, often described as a delicious and pleasant flavor perception. To enhance or complement the original flavor and meet the tastes of diverse regions, umami dipeptides have been extensively utilized in global food manufacturing. Currently, the application and purification techniques of dipeptides are relatively mature, while their umami mechanisms and molecular modification are both scarce. In this work, the 3D structure of the umami dipeptide target T1R1/T1R3 was first obtained through sequence alignment and homology modeling, then followed by the successful construction of a database containing 400 samples of dipeptides. Subsequently, the complex models of T1R1/T1R3, respectively, with DG (Asp-Gly) and EK (Glu-Lys) (i.e., T1R1_DG/T1R3, T1R1/T1R3_DG, T1R1_EK/T1R3, and T1R1/T1R3_EK) were obtained via molecular docking and virtual screening. Finally, based on comparative molecular dynamics (MD) simulation trajectories, the binding free energy was calculated to investigate receptor–ligand recognition and conformational changes, providing some implications for potential modifications of umami dipeptides. T1R1 tends to bind relatively small umami dipeptides, whereas T1R3 does the opposite, both of which favor the recognition of acidic and hydrophilic dipeptides. By comparing strategies such as hydroxyl introduction and chain length alteration, electrostatic effects may be more important than non-polar effects in molecular design. This work not only explores the recognition mechanism of umami dipeptides with the receptor T1R1/T1R3 showing certain theoretical significance, but also provides feasible suggestions for dipeptide screening and modification having certain application value.https://www.mdpi.com/1420-3049/30/13/2774umami dipeptideT1R1/T1R3molecular dynamics simulationmolecular recognitionmolecular modification
spellingShingle Kaixuan Hu
Guangzhou Sun
Wentong Yu
Mengyu Zhang
Shuang Wang
Yujie Cao
Dongling Hu
Li Liang
Gang He
Jianping Hu
Wei Liu
Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
Molecules
umami dipeptide
T1R1/T1R3
molecular dynamics simulation
molecular recognition
molecular modification
title Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
title_full Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
title_fullStr Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
title_full_unstemmed Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
title_short Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
title_sort molecular recognition and modification strategies of umami dipeptides with t1r1 t1r3 receptors
topic umami dipeptide
T1R1/T1R3
molecular dynamics simulation
molecular recognition
molecular modification
url https://www.mdpi.com/1420-3049/30/13/2774
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