Microsecond MD Simulations to Explore the Structural and Energetic Differences between the Human RXRα-PPARγ vs. RXRα-PPARγ-DNA
Abstract
:1. Introduction
2. Results
2.1. Stability of the Simulated RXRα-PPARγ-DNA and RXRα-PPARγ Systems
2.2. RMSF Analysis of the Simulated RXRα-PPARγ-DNA and RXRα-PPARγ Systems
2.3. Ligand Interactions of the PPARγ-RXRα-DNA System
2.3.1. RZG at the PPARγ Binding Pocket
2.3.2. 9CR at the RXRα Binding Pocket
2.4. Ligand Interactions of the RXRα-PPARγ System
2.4.1. RZG at the PPARγ Binding Pocket
2.4.2. 9CR at the RXRα Binding Pocket
2.5. The Protein–Protein Interactions of the RXRα-PPARγ-DNA and RXRα-PPARγ Systems
2.6. Binding Free Energy Calculations of Protein-Ligand Interactions Using MMGBSA
2.7. Binding Free Energy Calculations of Protein-Protein Interactions Using MMGBSA
2.8. Per-Residue Free Energy Decomposition
2.8.1. Per-Residue Free Energy Decomposition of the PPARγRZG Complex
2.8.2. Per-Residue Free Energy Decomposition of the RXRα9CR Complex
2.8.3. Per-Residue Free Energy Decomposition of the RXRα-PPARγ System
2.9. PCA
2.10. Dynamic Correlated Motions
3. Discussion
4. Material and Methods
4.1. System Setup
4.2. MD Simulations
4.3. MD Trajectory Analysis
Binding Free Energy Calculations
5. 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 | ΔEvdw | ΔEele | ΔGele,sol | ΔGnpol,sol | ΔGmmgbsa |
---|---|---|---|---|---|
Protein-ligand | |||||
PPARγRSG-RXRα9CR | |||||
PPARγRZG | −48.65 ± 3.0 | −18.47 ± 6.5 | 32.82 ± 4.0 | −6.56 ± 0.2 | −40.86 ± 5.0 |
RXRα9CR | −38.94 ± 3.0 | 43.78 ± 10.0 | −29.38 ± 9.9 | −5.49 ± 0.3 | −30.04 ± 3.0 |
PPARγ9CR-RXRα9CR-DNA | |||||
PPARγRZG | −51.33 ± 3.0 | −17.88 ± 6.0 | 33.23 ± 3.0 | −6.80 ± 0.3 | −42.78 ± 5.0 |
RXRα9CR | −45.99 ± 2.5 | 211.83 ± 13.0 | −198.96 ± 12.0 | −6.41 ± 0.2 | −39.43 ± 4.0 |
Protein-protein | |||||
PPARγRZG-RXRα9CR | −277.48 ± 15.0 | −1245.50 ± 133.5 | 1446.38 ± 133.0 | −42.98 ± 2.3 | −119.59 ± 18.0 |
PPARγRZG-RXRα9CR-DNA | −242.90 ± 12.0 | −750.53 ± 110.0 | 935.68 ± 107.0 | −37.09 ± 1.8 | −94.84 ± 13.0 |
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Azam, F.; Bello, M. Microsecond MD Simulations to Explore the Structural and Energetic Differences between the Human RXRα-PPARγ vs. RXRα-PPARγ-DNA. Molecules 2022, 27, 5778. https://doi.org/10.3390/molecules27185778
Azam F, Bello M. Microsecond MD Simulations to Explore the Structural and Energetic Differences between the Human RXRα-PPARγ vs. RXRα-PPARγ-DNA. Molecules. 2022; 27(18):5778. https://doi.org/10.3390/molecules27185778
Chicago/Turabian StyleAzam, Faizul, and Martiniano Bello. 2022. "Microsecond MD Simulations to Explore the Structural and Energetic Differences between the Human RXRα-PPARγ vs. RXRα-PPARγ-DNA" Molecules 27, no. 18: 5778. https://doi.org/10.3390/molecules27185778