The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations
Abstract
:1. Introduction
2. Results and Discussion
2.1. EGCG Significantly Diminishes the β-Sheet Propensity of Aβ-hIAPP Heterodimers
2.2. EGCG Attenuates the Aggregation Propensity of Both Aβ and hIAPP in Their Amyloid Core Regions
2.3. Polar and Aromatic Residues Serve as the Primary Binding Sites for EGCG within Both Aβ and hIAPP
2.4. The Interactions between EGCG and Aβ-hIAPP Heterodimers Primarily Involve H-Bond Interaction, π–π Stacking and Cation–π Interaction
2.5. EGCG Attenuates Both Inter-Chain Interaction between Aβ and hIAPP, as Well as the Intra-Chain Long-Range Interaction of Their Respective Peptides within Aβ-hIAPP Heterodimers
3. Materials and Methods
3.1. System Modeling
3.2. Simulation Details
3.3. Analysis Methods
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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System | Aβ-hIAPP | Aβ-hIAPP-EGCG |
---|---|---|
Number of replicas | 48 | |
Temperature range | 308.20–400.00 K | |
Simulation time | 500 ns | 600 ns |
Number of atoms | 40,522 | 40,447 |
Number of water molecules | 13,094 | 12,899 |
Box size | 7.5 × 7.5 × 7.5 nm3 | |
Number of EGCG | --- | 10 |
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Li, X.; Zhang, Y.; Yang, Z.; Zhang, S.; Zhang, L. The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations. Int. J. Mol. Sci. 2024, 25, 1636. https://doi.org/10.3390/ijms25031636
Li X, Zhang Y, Yang Z, Zhang S, Zhang L. The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2024; 25(3):1636. https://doi.org/10.3390/ijms25031636
Chicago/Turabian StyleLi, Xuhua, Yu Zhang, Zhiwei Yang, Shengli Zhang, and Lei Zhang. 2024. "The Inhibition Effect of Epigallocatechin-3-Gallate on the Co-Aggregation of Amyloid-β and Human Islet Amyloid Polypeptide Revealed by Replica Exchange Molecular Dynamics Simulations" International Journal of Molecular Sciences 25, no. 3: 1636. https://doi.org/10.3390/ijms25031636