Modeling the Tertiary Structure of the Rift Valley Fever Virus L Protein
Abstract
:1. Introduction
2. Results
2.1. Domain Identification
2.2. Modeling the Structure of RVFV L Protein Domains
2.3. Assembled L Protein Full-Length Structural Models
2.4. Energetic Refinement of Full-Length RVFV L-Protein Model Structures and Their Properties
3. Discussion
4. Materials and Methods
4.1. Domain Identification
4.2. Domain-Structure Modeling
4.3. All-Atom Molecular-Dynamics Investigation, Structural Relaxation, and Energetics Evaluation
4.4. Assembling Structural Models of Single Domains into a Full-Length Tertiary Structure
4.5. Tertiary-Structure Refinement
4.6. Tertiary-Structure Evaluation
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
aa | amino acid |
AZT | Azidothymidine |
CASP | Critical Assessment of Protein Structure Prediction |
CDC | Centers for Disease Control and Prevention |
Cryo TEM | Transmission electron cryomicroscopy |
FDA | U.S. Food and Drug Administration |
HIV | Human immunodeficiency virus |
lRMSD | least root-mean-squared-deviation |
MD | Molecular Dynamics |
NMR | Nuclear magnetic resonance |
NP | Nucleoprotein |
PAGE | Polyacrylamide gel electrophoresis |
PDB | Protein Data Bank |
PE | Potential energy |
RdRp | RNA dependent RNA polymerase |
RMSD | Root-mean-square deviation |
RVFV | Rift Valley Fever Virus |
SASA | Solvent Accesible Surface Area |
SDS | Sodium dodecyl sulfate |
USDA | U.S. Department of Agriculture |
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Sample Availability: The coordinates of the 12 predicted tertiary structure models are enclosed in the
Supplementary Materials. |
PDB id | Organism | C-Score | PDB id | Organism | C-Score | Model | Description | C-Score |
---|---|---|---|---|---|---|---|---|
L1-nt | - | −4.32 | L2-nt | - | −0.09 | L3-nt | I-TASSER model | −1.68 |
L1-4miw | Lassa virus | −1.55 | L2-5amq | La Crosse | 0.07 | L3-nt-MD | L3-nt with MD aa 1861–2092 | −1.95 |
L1-5ize | Hantaan virus | −0.97 | L2-5amr | La Crosse | −0.09 | L3-AIDA | L3-nt-MD, AIDA | - |
L1-5hsb | Andes virus | −0.74 | L2-1yuy | Hepatitis C | −0.05 | L3-Chimera | L3-nt-MD, Chimera | - |
L1-5j1n | Lassa virus | −1.45 | L2-4xhi | Thosea Asigna | 0.04 | |||
L1-MD | - | - | L2-4ucy | Metapneu- movirus | 0.17 |
Domain Segment | PE (kJ/mol) | (nm) | (nm) | (nm) |
---|---|---|---|---|
L1-MD | −8.62 | 6.66 | 3.05 | 6.03 |
L3 | −7.57 | 7.23 | 2.45 | 5.47 |
L3-MD | −8.70 | 3.89 | 2.97 | 5.11 |
MP-Score | Clash-Score | Rot-Out | Ram-Out | Ram-fv | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Model | Before min | After min | Before min | After min | Before min | After min | Before min | After min | Before min | After min |
L1-5ize + L2-4xhi + L3-nt | 3.75 | 2.48 | 74.1 | 1.89 | 7.91 | 8.52 | 8.42 | 7.22 | 80.53 | 72.16 |
L1-5ize + L2-4xhi + L3-MD | 3.70 | 2.52 | 73.34 | 1.95 | 7.53 | 9.68 | 7.85 | 6.96 | 82.54 | 78.54 |
L1-5ize + L2-4xhi + L3-AIDA | 3.79 | 2.49 | 73.36 | 1.71 | 8.82 | 9.18 | 9.76 | 8.40 | 80.05 | 71.19 |
L1-5ize + L2-4xhi + L3-Chimera | 3.91 | 2.60 | 88.81 | 2.04 | 9.84 | 10.95 | 10.07 | 7.47 | 79.58 | 70.82 |
L1-5hsb + L2-4xhi + L3-nt | 3.76 | 2.64 | 77.25 | 2.61 | 8.02 | 10.12 | 8.18 | 7.27 | 81.15 | 72.94 |
L1-5hsb + L2-4xhi + L3-MD | 3.73 | 2.50 | 74.62 | 1.98 | 8.23 | 9.07 | 7.70 | 7.22 | 83.16 | 73.20 |
L1-5hsb + L2-4xhi + L3-AIDA | 3.78 | 2.56 | 77.23 | 2.16 | 8.23 | 9.40 | 9.33 | 6.96 | 80.19 | 71.39 |
L1-5hsb + L2-4xhi + L3-Chimera | 3.90 | 2.56 | 89.62 | 2.13 | 9.36 | 9.13 | 9.73 | 7.89 | 79.29 | 69.43 |
L1-MD + L2-4xhi + L3-nt | 3.73 | 2.60 | 72.28 | 2.16 | 8.02 | 10.90 | 7.94 | 6.24 | 81.53 | 72.37 |
L1-MD + L2-4xhi + L3-MD | 3.70 | 2.49 | 76.02 | 1.86 | 7.42 | 9.18 | 7.42 | 6.86 | 83.43 | 72.89 |
L1-MD + L2-4xhi + L3-AIDA | 3.77 | 2.53 | 72.81 | 1.89 | 8.66 | 9.79 | 9.04 | 7.68 | 80.57 | 71.75 |
L1-MD + L2-4xhi + L3-Chimera | 3.90 | 2.57 | 90.22 | 2.28 | 9.63 | 9.07 | 10.16 | 8.45 | 80.30 | 70.36 |
Model | PE (kJ/mol) | (nm) | (nm) | (nm) | SASA (nm) | RMSD (nm) | ||
---|---|---|---|---|---|---|---|---|
1 | L1-MD + L2-4xhi + L3-nt | −6.664 | 5.10 | 9.49 | 0.05 ± 0.01 | 2.58 | 845.0 | 3.15 |
2 | L1-5ize + L2-4xhi + L3-nt | −6.710 | 5.29 | 9.51 | 2.05 ± 0.23 | 16.27 | 832.4 | 3.55 |
3 | L1-5hsb + L2-4xhi + L3-nt | −6.751 | 4.34 | 8.67 | 0.25 ± 0.03 | 5.64 | 816.0 | 3.37 |
4 | L1-5ize + L2-4xhi + L3-AIDA | −6.762 | 4.91 | 9.27 | 1.61 ± 0.18 | 14.33 | 802.8 | 3.74 |
5 | L1-MD + L2-4xhi + L3-MD | −6.781 | 4.78 | 9.15 | 0.17 ± 0.02 | 4.71 | 826.7 | 3.14 |
6 | L1-5ize + L2-4xhi + L3-MD | −6.791 | 5.11 | 9.44 | 0.48 ± 0.05 | 7.88 | 840.0 | 3.49 |
7 | L1-5hsb + L2-4xhi + L3-MD | −6.792 | 4.87 | 9.12 | 1.78 ± 0.19 | 15.04 | 801.5 | 3.55 |
8 | L1-5ize + L2-4xhi + L3-Chimera | −6.799 | 4.66 | 8.84 | 0.24 ± 0.03 | 5.60 | 759.8 | 1.85 |
9 | L1-5hsb + L2-4xhi + L3-Chimera | −6.820 | 4.71 | 8.99 | 0.54 ± 0.06 | 8.41 | 742.8 | 1.50 |
10 | L1-5hsb + L2-4xhi + L3-AIDA | −6.833 | 4.72 | 8.89 | 1.72 ± 0.18 | 14.80 | 771.0 | 3.31 |
11 | L1-MD + L2-4xhi + L3-AIDA | −6.901 | 4.43 | 8.71 | 0.66 ± 0.08 | 9.26 | 787.3 | 2.54 |
12 | L1-MD + L2-4xhi + L3-Chimera | −6.919 | 4.81 | 8.91 | 0.22 ± 0.02 | 5.28 | 747.6 | 0.00 |
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Gogovi, G.K.; Almsned, F.; Bracci, N.; Kehn-Hall, K.; Shehu, A.; Blaisten-Barojas, E. Modeling the Tertiary Structure of the Rift Valley Fever Virus L Protein. Molecules 2019, 24, 1768. https://doi.org/10.3390/molecules24091768
Gogovi GK, Almsned F, Bracci N, Kehn-Hall K, Shehu A, Blaisten-Barojas E. Modeling the Tertiary Structure of the Rift Valley Fever Virus L Protein. Molecules. 2019; 24(9):1768. https://doi.org/10.3390/molecules24091768
Chicago/Turabian StyleGogovi, Gideon K., Fahad Almsned, Nicole Bracci, Kylene Kehn-Hall, Amarda Shehu, and Estela Blaisten-Barojas. 2019. "Modeling the Tertiary Structure of the Rift Valley Fever Virus L Protein" Molecules 24, no. 9: 1768. https://doi.org/10.3390/molecules24091768
APA StyleGogovi, G. K., Almsned, F., Bracci, N., Kehn-Hall, K., Shehu, A., & Blaisten-Barojas, E. (2019). Modeling the Tertiary Structure of the Rift Valley Fever Virus L Protein. Molecules, 24(9), 1768. https://doi.org/10.3390/molecules24091768