Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding
Abstract
:1. Introduction
2. Materials and Methods
2.1. Martini CG Simulations
2.2. Analyses
2.3. Association Rate Calculations Based on First Passage Time to Bound State
3. Results and Discussion
3.1. Linker Flexibility Impacts CaM/CaMBR Assembly
3.2. Linker Flexibility Determines the CaM Conformation Ensemble
3.3. Higher Linker Flexibility Attenuates the Sensitivity of the Association Rate to Ionic Strength
4. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CaM | Calmodulin |
CaN | Calcineurin |
CaMBR | CaM Binding Region |
CG | Coarse-Grained |
MD | Molecular Dynamics |
COM | Center of Mass |
RMSD | Root Mean Square Deviation |
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WT Linker | Labile Linker | |||||
---|---|---|---|---|---|---|
0 M | 0.15 M | 0.5 M | 0 M | 0.15 M | 0.5 M | |
T (ns) | 1247.78 ± 0.05 | 1708.28 ± 0.06 | 2326.98 ± 0.05 | 1441.32 ± 0.06 | 1930.28 ± 0.06 | 2178.93 ± 0.06 |
(10 M s, 300 K) a | 16.29 ± 0.92 | 11.90 ± 0.70 | 8.73 ± 0.46 | 14.10 ± 0.85 | 10.53 ± 0.60 | 9.33 ± 0.53 |
Expt. (10 M s, 310 K) b | 2.2 ± 0.44 |
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Sun, B.; Kekenes-Huskey, P.M. Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding. Int. J. Mol. Sci. 2021, 22, 4990. https://doi.org/10.3390/ijms22094990
Sun B, Kekenes-Huskey PM. Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding. International Journal of Molecular Sciences. 2021; 22(9):4990. https://doi.org/10.3390/ijms22094990
Chicago/Turabian StyleSun, Bin, and Peter M. Kekenes-Huskey. 2021. "Assessing the Role of Calmodulin’s Linker Flexibility in Target Binding" International Journal of Molecular Sciences 22, no. 9: 4990. https://doi.org/10.3390/ijms22094990