Exploring Large Domain Motions in Proteins Using Atomistic Molecular Dynamics with Enhanced Conformational Sampling
Abstract
1. Introduction
2. Results
2.1. Structures of RBPG134R in the Apo and Holo States
2.2. gREST_SSCR Simulations of RBPG134R in the Apo and Holo States
2.2.1. How gREST_SSCR Works in RBPG134R Simulations
2.2.2. Comparison of Conformational Sampling Abilities between cMD and gREST_SSCR
2.2.3. Intermediate Structures of RBPG134R Stabilized by the Inter-Domain Salt-Bridge Interactions
3. Discussion
3.1. How gREST_SSCR Can Enhance Conformational Sampling of Large-Scale Domain Motions of Proteins
3.2. Molecular Mechanisms Underlying Ligand-Induced Conformational Changes of RBP
3.3. General Applications of gREST and gREST_SSCR
4. Materials and Methods
4.1. Modeling of RBPG134R for MD Simulations
4.2. cMD Simulations
4.3. gREST_SSCR Simulations
4.4. Simulation Trajectory Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MD | Molecular dynamics |
gREST | Generalized replica exchange with solute tempering |
gREST_SSCR | gREST selected surface charged residues |
RBP | Ribose binding protein |
NTD | N-terminal domain |
CTD | C-terminal domain |
Rg | Radius of gyration |
RMSD | Root mean square deviation |
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Method (State) | gREST_SSCR (Holo) | gREST_SSCR (Apo) | cMD (Holo) | cMD (Apo) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Residue (domain) | Residue (domain) | HC | HCL | HOL | HO | AOL | AO | All | HC | All | AT |
Asp67 * (NTD) | Arg134 * (CTD) | 82.8 ± 1.4 | 5.0 ± 0.6 | 0 | 0 | 0 | 0 | 47.7 ± 3.8 | 79.8 ± 1.1 | <0.1 | 0 |
Asp69 * (NTD) | Arg134 * (CTD) | 19.4 ± 1.3 | 78.0 ± 2.4 | 30.2 ± 4.5 | <0.4 | <0.1 | <0.1 | 19.0 ± 1.8 | 16.0 ± 0.8 | <0.1 | 0 |
Asp69 (NTD) | Arg139 (CTD) | 23.5 ± 1.0 | <0.5 | 0 | 0 | 0.1 | 0 | 18.0 ± 2.5 | 39.7 ± 2.4 | 0 | <0.1 |
Arg90 (NTD) | Glu140 (CTD) | 0 | 0 | 0 | 0 | 86.8 ± 0.9 | <1.1 | 11.8 ± 3.0 | 0 | 1.8 ± 0.3 | 74.5 |
Arg90 (NTD) | Asp215 (CTD) | 0 | 0 | <0.5 | 34.8 ± 4.2 | 0 | 37.2 ± 3.9 | 0 | 0 | 30.9 ± 2.3 | 0 |
Glu140 (CTD) | Lys260 (Hinge) | 3.9 ± 0.3 | 44.5 ± 3.8 | 80.4 ± 1.2 | 79.2 ± 1.4 | <0.7 | 59.0 ± 3.5 | 6.7 ± 1.3 | 3.6 ± 0.1 | 62.4 ± 1.1 | 0 |
Glu221 (CTD) | Lys266 (Hinge) | 24.0 ± 1.2 | 26.9 ± 1.1 | <0.2 | 0 | <0.6 | <0.3 | 19.4 ± 1.8 | 31.2 ± 0.8 | <0.3 | 0 |
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Dokainish, H.M.; Sugita, Y. Exploring Large Domain Motions in Proteins Using Atomistic Molecular Dynamics with Enhanced Conformational Sampling. Int. J. Mol. Sci. 2021, 22, 270. https://doi.org/10.3390/ijms22010270
Dokainish HM, Sugita Y. Exploring Large Domain Motions in Proteins Using Atomistic Molecular Dynamics with Enhanced Conformational Sampling. International Journal of Molecular Sciences. 2021; 22(1):270. https://doi.org/10.3390/ijms22010270
Chicago/Turabian StyleDokainish, Hisham M., and Yuji Sugita. 2021. "Exploring Large Domain Motions in Proteins Using Atomistic Molecular Dynamics with Enhanced Conformational Sampling" International Journal of Molecular Sciences 22, no. 1: 270. https://doi.org/10.3390/ijms22010270
APA StyleDokainish, H. M., & Sugita, Y. (2021). Exploring Large Domain Motions in Proteins Using Atomistic Molecular Dynamics with Enhanced Conformational Sampling. International Journal of Molecular Sciences, 22(1), 270. https://doi.org/10.3390/ijms22010270