The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation
Abstract
:1. Introduction
2. Results
2.1. Self-Assembly of the GpA-Transmembrane Region Reconstructs the NMR Interface with Low Frequency
2.2. Interface Frequencies Are Depend on Different Fatty Acid Chain Environments
Lipid | a | b | c | d | Lim |
---|---|---|---|---|---|
DUPC-DUPC | 0.51 | 0.10 | 0.42 | 0.02 | 0.93 |
DUPC-DPPC | 0.37 | 0.07 | 0.18 | 0.01 | 0.56 |
DUPC-POPC | 0.24 | 0.09 | 0.12 | 0.01 | 0.36 |
DUPC-DOPC | 0.18 | 0.11 | 0.07 | 0.02 | 0.25 |
DUPC-DSCP | 0.18 | 0.10 | 0.09 | 0.02 | 0.27 |
DPPC-DPPC | 0.55 | 0.07 | 0.38 | 0.01 | 0.94 |
DPPC-POPC | 0.58 | 0.07 | 0.24 | 0.01 | 0.82 |
DPPC-DOPC | 0.58 | 0.08 | 0.22 | 0.01 | 0.80 |
DPPC-DSPC | 0.57 | 0.07 | 0.22 | 0.01 | 0.79 |
POPC-POPC | 0.59 | 0.09 | 0.36 | 0.02 | 0.95 |
POPC-DOPC | 0.73 | 0.08 | 0.20 | 0.01 | 0.93 |
POCP-DSPC | 0.67 | 0.08 | 0.25 | 0.01 | 0.92 |
DOPC-DOPC | 0.65 | 0.13 | 0.31 | 0.02 | 0.96 |
DOPC-DSPC | 0.73 | 0.09 | 0.19 | 0.01 | 0.93 |
DSPC-DSPC | 0.59 | 0.11 | 0.35 | 0.02 | 0.95 |
2.3. Transitions between Dimer Conformations Are Visited by Long Self-Assembly Simulations
2.4. Stability of the NMR Interface Depends on Helix Length and Helix Conformation
2.5. Correction of the Helix Conformation Leads to Increased NMR Interface Frequency
bb5 | None | 500 | 1000 | 5000 | 10000 | bb3 | |
---|---|---|---|---|---|---|---|
bb4 | |||||||
None | 133.07 | 115.7 | 100.2 | 60.34 | 57.02 | None | |
500 | 137.10 | 123.6 | 114.4 | 72.56 | 62.92 | ||
1000 | 121.99 | 114.0 | 104.0 | 70.09 | 62.57 | ||
5000 | 83.59 | 84.61 | 82.69 | 73.35 | 71.52 | ||
10,000 | 75.11 | 77.43 | 76.97 | 76.83 | 79.96 | ||
None | 71.72 | 61.61 | 51.89 | 40.38 | 44.57 | 500 | |
500 | 92.88 | 83.73 | 70.28 | 51.18 | 50.20 | ||
1000 | 81.57 | 78.54 | 69.55 | 51.53 | 52.24 | ||
5000 | 58.17 | 60.20 | 60.39 | 61.08 | 63.49 | ||
10,000 | 64.70 | 66.86 | 67.18 | 73.00 | 76.51 | ||
None | 54.63 | 56.27 | 45.74 | 39.17 | 47.65 | 1000 | |
500 | 87.97 | 79.35 | 69.90 | 50.15 | 50.48 | ||
1000 | 75.77 | 72.60 | 65.51 | 51.49 | 52.83 | ||
5000 | 56.98 | 60.49 | 59.77 | 60.89 | 63.18 | ||
10,000 | 64.17 | 67.19 | 66.17 | 72.05 | 76.92 | ||
None | 27.38 | 32.15 | 34.26 | 46.53 | 57.14 | 5000 | |
500 | 48.72 | 50.96 | 49.47 | 50.73 | 56.61 | ||
1000 | 49.67 | 49.56 | 49.15 | 51.87 | 59.93 | ||
5000 | 53.08 | 56.04 | 55.63 | 63.25 | 71.04 | ||
10,000 | 67.34 | 68.75 | 68.40 | 75.04 | 80.79 | ||
None | 32.34 | 33.56 | 37.52 | 55.03 | 64.71 | 10,000 | |
500 | 38.60 | 41.83 | 45.41 | 53.83 | 65.94 | ||
1000 | 40.73 | 44.60 | 46.12 | 57.61 | 66.66 | ||
5000 | 59.00 | 60.18 | 59.61 | 69.77 | 75.88 | ||
10,000 | 71.35 | 71.95 | 73.49 | 79.16 | 84.68 |
Place | DUPC | DPPC | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
m22 | m22 + bb3 | GpA2010 | m22 | m22 + bb3 | GpA2010 | |||||||
nr | freq | nr | freq | nr | freq | nr | freq | nr | freq | nr | freq | |
1 | 81 | 17.0% | 81 | 13.3% | 2 | 31.3% | 63 | 15.0% | 52 | 19.7% | 2 | 15.7% |
2 | 76 | 11.7% | NMR | 10.3% | 0 | 19.3% | 52 | 11.0% | 63 | 12.7% | 0 | 11.7% |
3 | 16 | 11.3% | 76 | 9.3% | 12 | 12.3% | 79 | 8.7% | 42 | 8.0% | 7 | 10.0% |
4 | 79 | 6.3% | 33 | 6.7% | 16 | 4.7% | 42 | 7.3% | 76/79 | 5.0% | 6 | 6.7% |
5 | NMR | 6.0% | 16/79 | 6.0% | 6/9 | 3.0% | 81/12 | 6.0% | 12 | 4.3% | 12 | 6.0% |
3. Discussion
4. Methods
4.1. Simulation Details
4.2. System Composition
4.3. Details for the Short Self-Assembly Simulations
4.4. Description of the Similarity to the NMR Structure and Clustering of Results
4.5. Autocorrelation, Correlation and Fitting
4.6. Construction of the Transition Net
4.7. Backmapping and Comparison to NOE’s
5. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Flinner, N.; Mirus, O.; Schleiff, E. The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation. Int. J. Mol. Sci. 2014, 15, 14247-14268. https://doi.org/10.3390/ijms150814247
Flinner N, Mirus O, Schleiff E. The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation. International Journal of Molecular Sciences. 2014; 15(8):14247-14268. https://doi.org/10.3390/ijms150814247
Chicago/Turabian StyleFlinner, Nadine, Oliver Mirus, and Enrico Schleiff. 2014. "The Influence of Fatty Acids on the GpA Dimer Interface by Coarse-Grained Molecular Dynamics Simulation" International Journal of Molecular Sciences 15, no. 8: 14247-14268. https://doi.org/10.3390/ijms150814247