Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein

• Autor(a) principal: Valente, Renan Patrick de Penha
• Data de Publicação: 2020
• Outros Autores: Souza, Rafael Conceição de, Muniz, Gabriela de Medeiros, Ferreira, João Elias Vidueira, Miranda, Ricardo Morais de, Lima, Anderson Henrique Lima e, Vianez Júnior, João Lídio da Silva Gonçalves
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
• Texto Completo: https://patua.iec.gov.br/handle/iec/4110
• topic: Vírus do Nilo Ocidental / isolamento & purificação; Proteínas do Envelope Viral; Mutação; Mapeamento de Epitopos; Simulação de Dinâmica Molecular

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.