Stability of Engineered Ferritin Nanovaccines Investigated by Combined Molecular Simulation and Experiments
| Autor: | Anton P. J. Middelberg, Bingyang Zhang, Lijie Wang, Jingxiu Bi, Yiran Qu, Yan Jiao, Yan Sun, Shuang Yin |
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| Rok vydání: | 2021 |
| Předmět: |
Nanoparticle
Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Epitope Molecular dynamics Protein stability Nanocages 0103 physical sciences Materials Chemistry Humans Thermal stability Physical and Theoretical Chemistry Vaccines 010304 chemical physics biology Protein Stability Chemistry Temperature 0104 chemical sciences Surfaces Coatings and Films Ferritin Ferritins Biophysics biology.protein Chemical stability Hydrophobic and Hydrophilic Interactions |
| Zdroj: | The Journal of Physical Chemistry B. 125:3830-3842 |
| ISSN: | 1520-5207 1520-6106 |
| Popis: | Human ferritin is regarded as an attractive and promising vaccine platform because of its uniform structure, good plasticity, and desirable thermal and chemical stabilities. Besides, it is biocompatible and presumed safe when used as a vaccine carrier. However, there is a lack of knowledge of how different antigen insertion sites on the ferritin nanocage impact the resulting protein stability and performance. To address this question, we selected Epstein-Barr nuclear antigen 1 as a model epitope and fused it at the DNA level with different insertion sites, namely, the N- and C-termini of ferritin, to engineer proteins E1F1 and F1E1, respectively. Protein properties including hydrophobicity and thermal, pH, and chemical stability were investigated both by molecular dynamics (MD) simulation and by experiments. Both methods demonstrate that the insertion site plays an important role in protein properties. The C-terminus insertion (F1E1) leads to a less hydrophobic surface and more tolerance to the external influence of high temperature, pH, and high concentration of chemical denaturants compared to N-terminus insertion (E1F1). Simulated protein hydrophobicity and thermal stability by MD were in high accordance with experimental results. Thus, MD simulation can be used as a valuable tool to engineer nanovaccine candidates, cutting down costs by reducing the experimental effort and accelerating vaccine design. |
| Databáze: | OpenAIRE |
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