Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α
Abstract
:1. Introduction
2. Methods
2.1. Preparation of PI3Kα and Liphagal
2.2. Docking Experiments
2.3. MD Simulations of the PI3Kα/Liphagal Complex
2.4. Binding Free Energy Calculations
2.5. Free Energy Decomposition
3. Results and Discussion
3.1. Docking Liphagal to the Crystal Structure of PI3Kα
3.2. Molecular Dynamics Simulation of Liphagal-Bound PI3Kα
3.3. Decomposition of Binding Energy on a Per-Residue Basis
3.4. Dynamics Analysis of the Interactions between PI3Kα and Liphagal
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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- Sample Availability: Samples of the calculations are available from the authors.
Energies | PI3Kα/Liphagal of Pose-A | PI3Kα/Liphagal of Pose-B | ||
---|---|---|---|---|
Mean (kcal·mol−1) | Std (kcal·mol−1) | Mean (kcal·mol−1) | Std (kcal·mol−1) | |
ΔEele | −50.06 | 4.05 | −7.51 | 1.81 |
ΔEvdw | −37.74 | 3.58 | −37.96 | 2.31 |
ΔEMM | −87.80 | 3.86 | −45.47 | 2.57 |
ΔGpb_sur | −5.65 | 0.22 | −5.94 | 0.22 |
ΔGpb | 58.84 | 3.05 | 29.82 | 3.55 |
ΔGpb_sol | 53.19 | 3.02 | 23.88 | 3.47 |
ΔGgb_sur | −5.65 | 0.22 | −5.94 | 0.22 |
ΔGgb | 54.95 | 2.44 | 22.66 | 1.71 |
ΔGgb_sol | 49.30 | 2.43 | 16.72 | 1.64 |
ΔHpb | −34.61 | 3.61 | −21.59 | 3.06 |
ΔHgb | −38.50 | 2.96 | −28.75 | 2.03 |
TΔS | −24.13 | 16.18 | −20.53 | 15.09 |
ΔGbind(pb) | −10.48 | −1.06 | ||
ΔGbind(gb) | −14.37 | −8.22 |
Inhibitor | Hydrogen Bond | Occupancy (%) | Distance (Å) | |
---|---|---|---|---|
Liphagal of Pose-A | PI3Kα | |||
Liphagal of pose-A | benzofuran ring 15-OH | O-Asp810 | 89.4 | 2.59 (0.09) |
benzofuran ring 16-OH | O-Asp810 | 87.4 | 2.59 (0.09) | |
benzofuran ring 16-O | OH-Tyr836 | 97.2 | 2.85 (0.15) | |
Liphagal of pose-B | Liphagal of pose-B | PI3Kα | ||
benzofuran ring 14-formyl-O | NH-Val851 | 70.0 | 3.05 (0.26) |
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Gao, Y.; Ma, Y.; Yang, G.; Li, Y. Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α. Molecules 2016, 21, 857. https://doi.org/10.3390/molecules21070857
Gao Y, Ma Y, Yang G, Li Y. Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α. Molecules. 2016; 21(7):857. https://doi.org/10.3390/molecules21070857
Chicago/Turabian StyleGao, Yanjuan, Ying Ma, Guangde Yang, and Yiping Li. 2016. "Molecular Dynamics Simulations to Investigate the Binding Mode of the Natural Product Liphagal with Phosphoinositide 3-Kinase α" Molecules 21, no. 7: 857. https://doi.org/10.3390/molecules21070857