Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein
The envelope (E) protein is an important target for antibodies in favivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a dir...
| Autor principal: | Valente, Renan Patrick de Penha |
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| Outros Autores: | Souza, Rafael Concei??o de, Muniz, Gabriela de Medeiros, Ferreira, Jo?o Elias Vidueira, Miranda, Ricardo Morais de, Lima, Anderson Henrique Lima e, Vianez J?nior, Jo?o L?dio da Silva Gon?alves |
| Grau: | Artigo |
| Idioma: | eng |
| Publicado em: |
Nature Research
2020
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| Assuntos: | |
| Acesso em linha: |
http://patua.iec.gov.br//handle/iec/4110 |
| Resumo: |
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The envelope (E) protein is an important target for antibodies in favivirus. Literature reports that
the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and
increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in
the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular
dynamics simulations, the efects of the T198F mutation in the fexibility of the E protein of WNV
and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed
that the mutation favors the formation of alternative hydrogen bonds, hampering the bending
movement between domains I and II. We hypothesized that this is the mechanism by which the T198F
mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred
conformation, rendering it more prone to recognition by antibodies. |