Identification of Direct Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by Structure-Based Virtual Screening and Molecular Docking Approach
Abstract
:1. Introduction
2. Results and Discussion
2.1. Sequence Alignment and Structural Comparison
2.2. Parameter Setting for Molecular Docking
2.3. High-Throughput Virtual Screening Procedure
2.4. Analysis of Binding Mode of Activators for α1β1γ1 AMPK Isoform
2.5. Analysis of Binding Mode of Activators for α2β1γ1 AMPK Isoform
2.6. Biological Activities
3. Materials and Methods
3.1. Sequence Alignment and Structural Comparison
3.2. Molecular Docking
3.3. High-Throughput Virtual Screening
3.4. The In Vitro Activation Assay
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Isoforms | Compound No. | Total-Score | Crash | Polar | Similarity | Number of HBA/HBD | MolLog P | Drug-Likeness Model Score |
---|---|---|---|---|---|---|---|---|
AMPK (α1β1γ1) activators | F064-1335 | 10.50 | −2.35 | 3.54 | 0.44 | 6/1 | 3.79 | −0.16 |
M5653-1884 | 10.24 | −1.43 | 2.90 | 0.50 | 5/1 | 6.07 | 0.22 | |
D454-0135 | 10.20 | −1.58 | 3.41 | 0.44 | 6/2 | 4.03 | −0.31 | |
M8006-4303 | 10.07 | −1.83 | 4.29 | 0.58 | 6/1 | 1.01 | 1.02 | |
F264-3019 | 9.93 | −1.39 | 3.19 | 0.46 | 6/1 | 5.44 | 1.00 | |
F377-1213 | 10.03 | −1.43 | 1.32 | 0.44 | 6/1 | 4.12 | 0.16 | |
PF-06409577 | 7.29 | −0.07 | 3.08 | 0.93 | 3/3 | 3.80 | 0.71 | |
AMPK (α2β1γ1) activators | L267-1138 | 10.96 | −2.46 | 2.78 | 0.52 | 4/1 | 6.05 | −0.08 |
F684-0053 | 10.60 | −2.77 | 4.31 | 0.54 | 7/3 | 2.04 | 0.54 | |
C804-0412 | 10.15 | −3.27 | 3.39 | 0.54 | 5/2 | 2.53 | 1.00 | |
M5976-1661 | 9.46 | −0.92 | 1.32 | 0.46 | 6/0 | 4.84 | 0.62 | |
M039-0295 | 9.35 | −1.61 | 1.48 | 0.50 | 6/1 | 2.66 | −0.20 | |
M5050-0116 | 9.27 | −1.35 | 2.82 | 0.49 | 7/2 | 5.13 | 0.38 | |
A-769662 | 7.44 | −1.46 | 1.26 | 0.93 | 5/3 | 3.46 | 0.30 | |
991 | 8.38 | −0.96 | 4.08 | 0.73 | 4/2 | 5.38 | 0.41 |
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Huang, T.; Sun, J.; Zhou, S.; Gao, J.; Liu, Y. Identification of Direct Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by Structure-Based Virtual Screening and Molecular Docking Approach. Int. J. Mol. Sci. 2017, 18, 1408. https://doi.org/10.3390/ijms18071408
Huang T, Sun J, Zhou S, Gao J, Liu Y. Identification of Direct Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by Structure-Based Virtual Screening and Molecular Docking Approach. International Journal of Molecular Sciences. 2017; 18(7):1408. https://doi.org/10.3390/ijms18071408
Chicago/Turabian StyleHuang, Tonghui, Jie Sun, Shanshan Zhou, Jian Gao, and Yi Liu. 2017. "Identification of Direct Activator of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by Structure-Based Virtual Screening and Molecular Docking Approach" International Journal of Molecular Sciences 18, no. 7: 1408. https://doi.org/10.3390/ijms18071408