Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments
Abstract
:1. Introduction
2. Results and Discussion
2.1. Inhibition of Batx-I Activity
2.2. Binding Modes in Unbiased Simulations
2.3. Binding of Triterpenes with Carboxylates at Position C-17
2.4. Two Binding Modes of Carboxylate–Zn
2.5. Free-Energy Barriers
2.6. The Role of Arg110
2.7. Thermodynamic Decomposition of Binding Free Energy
2.8. Binding of Betulin and -Boswellic Acid
3. Conclusions
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Purification of the Metalloproteinase Batx-I
4.3. Inhibition of Proteolytic Activity
4.4. Molecular Docking Methods
4.5. Molecular Dynamics Methods
4.6. Free Energy Calculations
4.7. Determination of Binding Enthalpy and Entropy
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ABF | Adaptive biasing force |
COLVARS | Colective variables |
EDTA | Ethylenediamine-tetraacetic acid |
FES | Free energy surface |
DTPA | Diethylene triamine pentaacetic acid |
MM-PBSA | Molecular-mechanics Poisson–Boltzmann surface area |
MM-GBSA | Molecular-mechanics Generalized Born surface area |
PMF | Potential of mean force |
RP-HPLC | Reverse phase-High-performance liquid chromatography |
SDS-PAGE | Sodium dodecyl sulfate polyacrylamide gel electrophoresis |
SVMPs | Snake venom metalloproteinases |
TPEN | N, N, N’, N’-Tetrakis (2-pyridylmethyl) ethane-1,2-diamine |
TTD | Tetraethylthiuram disulfide |
References
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Terpene | (M) | Experimental (kcal/mol) | Theoretical (kcal/mol) |
---|---|---|---|
Betulinic acid | |||
Ursolic acid | |||
Oleanolic acid | |||
Madecassic acid | ND | ||
Betulin | ND | ||
-Boswellic acid | ND | ND |
Free-Energy Minimum | (kcal/mol) | (kcal/mol) | (kcal/mol) | (kcal/mol) |
---|---|---|---|---|
A | ||||
B |
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Preciado, L.M.; Pereañez, J.A.; Azhagiya Singam, E.R.; Comer, J. Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments. Toxins 2018, 10, 397. https://doi.org/10.3390/toxins10100397
Preciado LM, Pereañez JA, Azhagiya Singam ER, Comer J. Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments. Toxins. 2018; 10(10):397. https://doi.org/10.3390/toxins10100397
Chicago/Turabian StylePreciado, Lina María, Jaime Andrés Pereañez, Ettayapuram Ramaprasad Azhagiya Singam, and Jeffrey Comer. 2018. "Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments" Toxins 10, no. 10: 397. https://doi.org/10.3390/toxins10100397