Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors
Abstract
1. Introduction
2. Results and Discussion
2.1. Construction of the T1R1/T1R3 Model
2.1.1. Moderate Sequence Similarity to the Template
2.1.2. High Structural Similarity to the Template
2.1.3. Rationality Evaluation of the T1R1/T1R3 Modeled Structure
2.2. Determination of Representative Umami Dipeptides
2.2.1. Construction of a Dipeptide Structure Database
2.2.2. Screening Strategies for Umami Dipeptides
2.3. Binding Modes of Umami Dipeptides EK and DG to Receptors T1R1/T1R3
2.4. Pocket Characteristics of T1R1/T1R3
2.4.1. The Pocket Size of T1R3 Is Significantly Larger than That of T1R1, Conditionally Incorporating Bigger Substrates
2.4.2. The T1R3 Pocket Is Generally Alkaline with a Larger Channel Radius
2.5. Molecular Dynamics Simulation of Umami Dipeptide Recognition with T1R1/T1R3
2.5.1. Trajectory Convergence Is a Prerequisite for Molecular Recognition and Conformational Change Analyses
2.5.2. The Binding of Umami Peptides Results in Conformational Closure of VFT
2.5.3. The Hydrophilic Pocket Facilitates the Binding of Umami Dipeptides
2.5.4. Stable Hydrogen Bonds Exist Between Umami Peptides and T1R1/T1R3
2.5.5. Weak Interactions Favor the Recognition of Umami Peptides by T1R1/T1R3
2.6. Molecular Optimization of Umami Dipeptides Driven by Binding Free Energy
2.6.1. Introduction of Hydroxyl Groups
2.6.2. Adjustment of Side-Chain Length
3. Materials and Methods
3.1. Homology Modeling
3.2. Construction of Dipeptide Structure Database
3.3. Molecular Docking and Virtual Screening
3.4. Molecular Dynamics Simulation
3.5. Conformational Clustering
3.6. Binding Free Energy Calculation
3.7. Weak Interaction Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Hu, K.; Sun, G.; Yu, W.; Zhang, M.; Wang, S.; Cao, Y.; Hu, D.; Liang, L.; He, G.; Hu, J.; et al. Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors. Molecules 2025, 30, 2774. https://doi.org/10.3390/molecules30132774
Hu K, Sun G, Yu W, Zhang M, Wang S, Cao Y, Hu D, Liang L, He G, Hu J, et al. Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors. Molecules. 2025; 30(13):2774. https://doi.org/10.3390/molecules30132774
Chicago/Turabian StyleHu, Kaixuan, Guangzhou Sun, Wentong Yu, Mengyu Zhang, Shuang Wang, Yujie Cao, Dongling Hu, Li Liang, Gang He, Jianping Hu, and et al. 2025. "Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors" Molecules 30, no. 13: 2774. https://doi.org/10.3390/molecules30132774
APA StyleHu, K., Sun, G., Yu, W., Zhang, M., Wang, S., Cao, Y., Hu, D., Liang, L., He, G., Hu, J., & Liu, W. (2025). Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors. Molecules, 30(13), 2774. https://doi.org/10.3390/molecules30132774