Computational Study on Substrate Specificity of a Novel Cysteine Protease 1 Precursor from Zea mays
Abstract
:1. Introduction
2. Results and Discussion
2.1. Homology Modeling
Template (PDB ID) | Sequence Identity | Resolution | Organism | Query Coverage | QMEAN Z-Score a | Procheck b | Errat c |
---|---|---|---|---|---|---|---|
1S4V A | 59% | 2.00 | Ricinus communis | 0.64 | −1.26 | 83.1% core 15.7% allow 0.6% gener 0.6% disall | 85.2 |
2FO5 A | 56% | 2.20 | Hordeum vulgare | 0.64 | −2.01 | 83.1% core 15.7% allow 0.6% gener 6.0% disall | 82.0 |
3P5W A | 55% | 1.90 | Actinidia arguta | 0.63 | −1.82 | 82.6% core 15.7% allow 0.6% gener 1.1% disall | 82.5 |
1AEC A | 53% | 1.86 | Actinidia chinensis | 0.63 | −2.38 | 83.6% core 15.3% allow 0.0% gener 1.1% disall | 82.8 |
1CJL A | 44% | 2.20 | Homo sapiens | 0.79 | −4.32 | 85.1% core 13.2% allow 0.4% gener 1.3% disall | 68.6 |
1PCI A | 43% | 3.20 | Carica papaya | 0.90 | −5.55 | 79.3% core 18.8% allow 1.5% gener 0.4% disall | 72.6 |
3TNX A | 42% | 2.62 | Carica papaya | 0.88 | −5.17 | 81.5% core 16.2% allow 1.5% gener 0.8% disall | 70.8 |
7PCK B | 40% | 3.20 | Homo sapiens | 0.89 | −4.91 | 78.8% core 17.8% allow 1.5% gener 1.9% disall | 63.0 |
2.2. Docking Study
2.2.1. Docking Validation
2.2.2. P1–S1 Interactions
Ligands | Docking Score | Ligands | Docking Score | Ligands | Docking Score |
---|---|---|---|---|---|
R-AMC | −10.4 | L-AMC | −6.4 | I-AMC | −6.1 |
F-AMC | −8.3 | V-AMC | −6.4 | K-AMC | −6.1 |
Y-AMC | −7.9 | A-AMC | −6.2 | T-AMC | −6.1 |
W-AMC | −7.5 | Q-AMC | −6.2 | M-AMC | −5.9 |
N-AMC | −7.2 | E-AMC | −6.2 | S-AMC | −5.9 |
P-AMC | −6.9 | G-AMC | −6.2 | D-AMC | −5.5 |
H-AMC | −6.4 | C-AMC | −6.1 | – | – |
2.2.3. P2–S2 Interactions
Ligands | Docking Score | Ligands | Docking Score | Ligands | Docking Score |
---|---|---|---|---|---|
F-R-AMC | −9.8 | A-R-AMC | −8.3 | E-R-AMC | −8.0 |
Y-R-AMC | −9.7 | N-R-AMC | −8.3 | T-R-AMC | −8.0 |
P-R-AMC | −8.9 | I-R-AMC | −8.3 | G-R-AMC | −7.8 |
H-R-AMC | −8.5 | D-R- AMC | −8.2 | K-R-AMC | −7.6 |
R-R-AMC | −8.4 | Q-R-AMC | −8.2 | M-R-AMC | −7.6 |
W-R-AMC | −8.4 | L-R-AMC | −8.1 | S-R-AMC | −7.6 |
V-R-AMC | −8.4 | C-R-AMC | −8.1 | – | – |
2.3. Structural Interaction Fingerprint Analysis
Amino Acid | Interactions | ||||||||
---|---|---|---|---|---|---|---|---|---|
Any | Back-Bone | Side Chain | Polar | Hydrophobic | H-Bond Acceptor | H-Bond Donor | Aromatic | Charged | |
Q143 | 1 | 0.1 | 1 | 0.97 | 0 | 0 | 0.71 | 0 | 0 |
W308 | 1 | 0.68 | 1 | 1 | 0 | 0 | 0.71 | 1 | 0 |
H285 | 0.97 | 0.65 | 0.97 | 0.97 | 0 | 0 | 0.1 | 0 | 0 |
M194 | 0.94 | 0 | 0.94 | 0 | 0.94 | 0 | 0 | 0 | 0 |
L283 | 0.94 | 0.71 | 0.94 | 0.74 | 0.19 | 0 | 0 | 0 | 0 |
G144 | 0.9 | 0.9 | 0 | 0.35 | 0.55 | 0 | 0 | 0 | 0 |
R268 | 0.9 | 0.9 | 0.97 | 0.87 | 0.1 | 0.19 | 0 | 0 | 0.71 |
A286 | 0.86 | 0.86 | 0.86 | 0.23 | 0 | 0 | 0 | 0 | 0 |
L193 | 0.74 | 0.71 | 0.74 | 0.23 | 0.52 | 0 | 0 | 0 | 0 |
G147 | 0.72 | 0.72 | 0 | 0.59 | 0.13 | 0 | 0 | 0 | 0 |
S311 | 0.68 | 0.55 | 0.68 | 0.55 | 0.19 | 0.1 | 0 | 0 | 0 |
D190 | 0.56 | 0.56 | 0.16 | 0.46 | 0.1 | 0.16 | 0 | 0 | 0 |
C189 | 0.56 | 0.56 | 0 | 0.1 | 0.46 | 0 | 0 | 0 | 0 |
G191 | 0.56 | 0.56 | 0 | 0.53 | 0 | 0 | 0 | 0 | 0 |
A286 | 0.56 | 0.56 | 0 | 0.56 | 0 | 0 | 0 | 0 | 0 |
C149 | 0.52 | 0.29 | 0.9 | 0.39 | 0.52 | 0 | 0.13 | 0 | 0 |
N284 | 0.45 | 0.45 | 0.19 | 0.42 | 0 | 0.1 | 0 | 0 | 0 |
D142 | 0.32 | 0 | 0.32 | 0.32 | 0 | 0.1 | 0 | 0 | 0 |
Y270 | 0.29 | 0.29 | 0 | 0.26 | 0 | 0.13 | 0 | 0 | 0 |
W150 | 0.26 | 0.26 | 0.26 | 0.19 | 0 | 0 | 0 | 0 | 0 |
G262 | 0.26 | 0.26 | 0 | 0.1 | 0.16 | 0 | 0 | 0 | 0 |
D271 | 0.23 | 0.23 | 0.23 | 0.1 | 0.16 | 0 | 0 | 0 | 0 |
2.4. Calculation of the Free Energy of Binding with Molecular Mechanics-Poisson–Boltzmann Surface Area (MM-PBSA) Method
Energy Components (kcal·mol−1) | R-AMC–zmCP1 | D-AMC–zmCP1 |
---|---|---|
∆Eele | −172.62 | −106.88 |
∆EvdW | −33.5 | −31.4 |
∆GPB | 170.65 | 129.89 |
∆Gnp | −5.44 | −5.46 |
Non-polar | −38.94 | −36.86 |
Polar | −1.97 | 23.01 |
∆Gbind | −40.91 | −13.85 |
3. Experimental Section
3.1. Homology Protein Modeling
3.2. Molecular Dynamics (MD) Simulation
3.3. Docking Study
3.4. Structural Interaction Fingerprint Analysis
3.5. MM-PBSA Calculations
4. Conclusions
Supplementary Files
Acknowledgments
Conflicts of Interest
References
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Liu, H.; Chen, L.; Li, Q.; Zheng, M.; Liu, J. Computational Study on Substrate Specificity of a Novel Cysteine Protease 1 Precursor from Zea mays. Int. J. Mol. Sci. 2014, 15, 10459-10478. https://doi.org/10.3390/ijms150610459
Liu H, Chen L, Li Q, Zheng M, Liu J. Computational Study on Substrate Specificity of a Novel Cysteine Protease 1 Precursor from Zea mays. International Journal of Molecular Sciences. 2014; 15(6):10459-10478. https://doi.org/10.3390/ijms150610459
Chicago/Turabian StyleLiu, Huimin, Liangcheng Chen, Quan Li, Mingzhu Zheng, and Jingsheng Liu. 2014. "Computational Study on Substrate Specificity of a Novel Cysteine Protease 1 Precursor from Zea mays" International Journal of Molecular Sciences 15, no. 6: 10459-10478. https://doi.org/10.3390/ijms150610459