Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein
Valente, Renan Patrick de Penha
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
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.
xmlui.dri2xhtml.METS-1.0.item-citationVALENTE, Renan Patrick de Penha et al. Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein. Scientific Reports, v. 10, n. 9625, 2020.
xmlui.dri2xhtml.METS-1.0.item-decsPrimaryVírus do Nilo Ocidental / isolamento & purificação
Proteínas do Envelope Viral
Mapeamento de Epitopos
Simulação de Dinâmica Molecular