Impacts of Mutations in the P-Loop on Conformational Alterations of KRAS Investigated with Gaussian Accelerated Molecular Dynamics Simulations
Abstract
:1. Introduction
2. Results and Discussion
2.1. Structural Fluctuations and Internal Dynamics of KRAS
2.2. Free Energy Profile of Mutation-Induced Conformational Transitions of KRAS
2.3. Dynamics Behavior Revealed by PCA
2.4. Interaction Network of GDP with KRAS
3. Theory and Methods
3.1. Preparation of Simulated Systems
3.2. GaMD Simulations
3.3. Principal Component Analysis
3.4. Dynamics Cross-Correlation Maps
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Hydrogen Bonds a | Occupancy (%) b | ||||
---|---|---|---|---|---|
Residue | GDP | WT | G12A | G12D | G12R |
K16-N-H | O2B | 99.9 | 99.9 | 99.2 | 99.9 |
A18-N-H | O2A | 99.4 | 98.5 | 83.4 | 99.2 |
G15-N-H | O2B | 98.8 | 99.2 | 99.2 | 99.1 |
S17-N-H | O3A | 98.1 | 99.8 | 85.6 | 99.6 |
G13-N-H | O1B | 96.8 | 97.7 | 92.7 | 98.7 |
V14-N-H | O2B | 41.2 | 30.6 | 32.3 | 30.1 |
N116-ND2-HD21 | N7 | 89.4 | 93.1 | 85.9 | 92.8 |
K117-NZ-HZ2 | O4’ | 20.3 | 16.9 | 11.8 | 23.7 |
S145-OG-HG | N1 | 64.1 | 60.3 | 61.5 | 60.5 |
K147-N-H | O6 | 86.8 | 85.2 | 83.9 | 87.1 |
A146-N-H | O6 | 60.8 | 63.1 | 67.3 | 61.7 |
D119-OD1 | N1-H1N | 97.6 | 80.1 | 88.5 | 95.1 |
D119-OD2 | N2-H21 | 95.6 | 83.6 | 78.1 | 92.4 |
V29-O | O2’-H2’ | 25.5 | 22.9 | 28.8 | 27.3 |
D30-OD1 | O2’-H2’ | 19.6 | 10.3 | 25.4 | 10.9 |
D30-OD2 | O3’-H3’ | 17.8 | 8.2 | 23.1 | 9.2 |
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Shi, S.; Zheng, L.; Ren, Y.; Wang, Z. Impacts of Mutations in the P-Loop on Conformational Alterations of KRAS Investigated with Gaussian Accelerated Molecular Dynamics Simulations. Molecules 2023, 28, 2886. https://doi.org/10.3390/molecules28072886
Shi S, Zheng L, Ren Y, Wang Z. Impacts of Mutations in the P-Loop on Conformational Alterations of KRAS Investigated with Gaussian Accelerated Molecular Dynamics Simulations. Molecules. 2023; 28(7):2886. https://doi.org/10.3390/molecules28072886
Chicago/Turabian StyleShi, Shuhua, Linqi Zheng, Yonglian Ren, and Ziyu Wang. 2023. "Impacts of Mutations in the P-Loop on Conformational Alterations of KRAS Investigated with Gaussian Accelerated Molecular Dynamics Simulations" Molecules 28, no. 7: 2886. https://doi.org/10.3390/molecules28072886