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