Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation
Abstract
:1. Introduction
2. Results
2.1. Analysis of 3D Structures of Pore Domains on hCav1.3 and hCav1.2
2.2. Molecular Dynamics Simulation of hCav1.3/Cav1.2-PYTs Complexes
2.3. Analysis of Binding Modes of Complex Systems
2.4. Verification of the Binding Mode
3. Discussion
4. Materials and Methods
4.1. Homology Modeling
4.2. Molecular Docking of PYTs to hCav1.3 and hCav1.2
4.3. Molecular Dynamics Simulations
4.4. Binding Energy Calculations and Decomposition by MM/GBSA
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Complexes | ΔEvdW | ΔEEL | ΔEGB | ΔESURF | ΔEtotal |
---|---|---|---|---|---|
hCav1.3-PYT06 | −43.11 | −3.85 | 18.06 | −5.05 | −33.95 |
hCav1.2-PYT06 | −28.73 | −4.55 | 18.20 | −3.68 | −18.77 |
hCav1.3-PYT22 | −44.44 | −4.56 | 18.95 | −5.14 | −35.19 |
hCav1.2-PYT22 | −37.14 | −3.77 | 15.73 | −4.48 | −29.66 |
hCav1.3-PYT65 | −36.04 | −5.34 | 19.27 | −4.44 | −26.56 |
hCav1.2-PYT65 | −32.76 | −9.78 | 21.44 | −4.25 | −25.35 |
Complexes | ΔEvdW | ΔEEL | ΔEGB | ΔESURF | ΔEtotal |
---|---|---|---|---|---|
hCav1.3-PYT108 | −38.49 | −4.64 | 16.21 | −5.09 | −32.01 |
hCav1.2-PYT108 | −34.87 | −2.84 | 18.25 | −4.37 | −23.84 |
hCav1.3-PYT103 | −42.42 | −15.25 | 26.89 | −5.11 | −35.90 |
hCav1.2-PYT103 | −38.34 | −2.00 | 13.78 | −4.23 | −30.78 |
hCav1.3-PYT67 | −32.77 | −10.40 | 24.22 | −4.07 | −23.02 |
hCav1.2-PYT67 | −35.24 | −5.16 | 18.60 | −4.18 | −25.99 |
Sample Availability: Not Available. | |
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Ye, Q.; Zhang, Z.; Zhang, W.; Ding, Y.; Zhao, F.; Zhang, J.; Song, Y. Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation. Molecules 2020, 25, 5440. https://doi.org/10.3390/molecules25225440
Ye Q, Zhang Z, Zhang W, Ding Y, Zhao F, Zhang J, Song Y. Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation. Molecules. 2020; 25(22):5440. https://doi.org/10.3390/molecules25225440
Chicago/Turabian StyleYe, Qi, Zhenyu Zhang, Wenying Zhang, Yushan Ding, Fan Zhao, Jinghai Zhang, and Yongbo Song. 2020. "Investigation of the Selectivity of L-Type Voltage-Gated Calcium Channels 1.3 for Pyrimidine-2,4,6-Triones Derivatives Based on Molecular Dynamics Simulation" Molecules 25, no. 22: 5440. https://doi.org/10.3390/molecules25225440