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: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , |
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 |
Resumo: | 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. |
id |
IEC-2_3f3c9aa235d5608aa7c2e0c3e01b0a6c |
---|---|
oai_identifier_str |
oai:patua.iec.gov.br:iec/4110 |
network_acronym_str |
IEC-2 |
network_name_str |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
repository_id_str |
|
spelling |
Valente, Renan Patrick de PenhaSouza, Rafael Conceição deMuniz, Gabriela de MedeirosFerreira, João Elias VidueiraMiranda, Ricardo Morais deLima, Anderson Henrique Lima eVianez Júnior, João Lídio da Silva Gonçalves2020-06-30T18:29:27Z2020-06-30T18:29:27Z2020VALENTE, 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, 2020.2045-2322https://patua.iec.gov.br/handle/iec/411010.1038/s41598-020-66344-8The 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.Evandro Chagas Institute, Federal University of Pará, Federal Institute of Education, Science and Technology of Pará, FAPESPA and CNPq.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil / Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Federal Institute of Education, Science and Technology of Pará. Tucuruí, PA, Brazil.Federal Institute of Education, Science and Technology of Pará. Tucuruí, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Laboratório de Planejamento e Desenvolvimento de Fármacos. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.engNature ResearchUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope proteininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleVírus do Nilo Ocidental / isolamento & purificaçãoProteínas do Envelope ViralMutaçãoMapeamento de EpitoposSimulação de Dinâmica Molecularinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdfUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdfapplication/pdf1799979https://patua.iec.gov.br/bitstreams/7ed89aae-1065-4d43-9b83-bd023084ad47/download762f046d2c6af88f49ab149ba3111e77MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/f0f0e74d-0bfb-4e1e-8f83-9700dfe015d4/download11832eea31b16df8613079d742d61793MD52TEXTUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdf.txtUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdf.txtExtracted texttext/plain27574https://patua.iec.gov.br/bitstreams/499eaaef-6227-4884-b5bd-8f8e754cda83/downloadd60bdf0aa1bc3251837c990a7318743dMD55THUMBNAILUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdf.jpgUsing accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein.pdf.jpgGenerated Thumbnailimage/jpeg6289https://patua.iec.gov.br/bitstreams/56c16bf5-d9f4-4191-84d3-28b172aed67c/download824e6b0d6f6ce0372b120f2ce8854137MD56iec/41102022-10-20 21:18:45.548oai:patua.iec.gov.br:iec/4110https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T21:18:45Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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 |
dc.title.pt_BR.fl_str_mv |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
title |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
spellingShingle |
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 Vírus do Nilo Ocidental / isolamento & purificação Proteínas do Envelope Viral Mutação Mapeamento de Epitopos Simulação de Dinâmica Molecular |
title_short |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
title_full |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
title_fullStr |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
title_full_unstemmed |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
title_sort |
Using accelerated molecular dynamics simulation to elucidate the effects of the T198F mutation on the molecular flexibility of the West Nile virus envelope protein |
author |
Valente, Renan Patrick de Penha |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Vírus do Nilo Ocidental / isolamento & purificação Proteínas do Envelope Viral Mutação Mapeamento de Epitopos Simulação de Dinâmica Molecular |
topic |
Vírus do Nilo Ocidental / isolamento & purificação Proteínas do Envelope Viral Mutação Mapeamento de Epitopos Simulação de Dinâmica Molecular |
description |
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. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-06-30T18:29:27Z |
dc.date.available.fl_str_mv |
2020-06-30T18:29:27Z |
dc.date.issued.fl_str_mv |
2020 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
VALENTE, 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. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4110 |
dc.identifier.issn.-.fl_str_mv |
2045-2322 |
dc.identifier.doi.-.fl_str_mv |
10.1038/s41598-020-66344-8 |
identifier_str_mv |
VALENTE, 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. 2045-2322 10.1038/s41598-020-66344-8 |
url |
https://patua.iec.gov.br/handle/iec/4110 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Nature Research |
publisher.none.fl_str_mv |
Nature Research |
dc.source.none.fl_str_mv |
reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
instname_str |
Instituto Evandro Chagas (IEC) |
instacron_str |
IEC |
institution |
IEC |
reponame_str |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
collection |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
bitstream.url.fl_str_mv |
https://patua.iec.gov.br/bitstreams/7ed89aae-1065-4d43-9b83-bd023084ad47/download https://patua.iec.gov.br/bitstreams/f0f0e74d-0bfb-4e1e-8f83-9700dfe015d4/download https://patua.iec.gov.br/bitstreams/499eaaef-6227-4884-b5bd-8f8e754cda83/download https://patua.iec.gov.br/bitstreams/56c16bf5-d9f4-4191-84d3-28b172aed67c/download |
bitstream.checksum.fl_str_mv |
762f046d2c6af88f49ab149ba3111e77 11832eea31b16df8613079d742d61793 d60bdf0aa1bc3251837c990a7318743d 824e6b0d6f6ce0372b120f2ce8854137 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC) |
repository.mail.fl_str_mv |
clariceneta@iec.gov.br || Biblioteca@iec.gov.br |
_version_ |
1787533058758410240 |