Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
Autor(a) principal: | |
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Data de Publicação: | 2017 |
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/2882 |
Resumo: | The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol). |
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Siqueira, Andrei SantosLima, Alex Ranieri JerônimoSouza, Rafael Conceição deSantos, Alberdan SilvaVianez Júnior, João Lídio da Silva GonçalvesGonçalves, Evonnildo Costa2017-11-24T18:56:15Z2017-11-24T18:56:15Z2017SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017.0006-291Xhttps://patua.iec.gov.br/handle/iec/288210.1016/j.bbrc.2017.06.160The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol).Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovações Tecnológicas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Naturais. Laboratórios de Investigação Sistemática em Biotecnologia e Biodiversidade Molecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovações Tecnológicas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.engElsevierAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAntivirais / farmacologiaProteínas de Bactérias / farmacologiaProteínas de Transporte / farmacologiaCianobactérias / químicaDengue / terapiaVírus da Dengue / efeitos de drogasLectinas / farmacologiaProteínas do Envelope Viral / metabolismoMutação PuntualLigação ProteicaSimulação de Dinâmica MolecularTemperatura Ambienteinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECLICENSElicense.txtlicense.txttext/plain; charset=utf-871https://patua.iec.gov.br/bitstreams/cde35862-78fa-4f5f-8080-50a29bf389b6/download52f1732ea66fbd1123abe39f5373b797MD52ORIGINALAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdfAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdfapplication/pdf135659https://patua.iec.gov.br/bitstreams/b71083f6-ad5f-4e91-a7c5-5c4d8cce8421/download5b176be161c72009488d702f404f2802MD53TEXTAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.txtAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.txtExtracted texttext/plain4813https://patua.iec.gov.br/bitstreams/05b02da3-1167-4063-90a0-f90d69176154/downloada7fd799765bcd59cf166692899228642MD56THUMBNAILAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.jpgAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.jpgGenerated Thumbnailimage/jpeg6090https://patua.iec.gov.br/bitstreams/87764e73-8ac3-4756-bf95-d12d38be19fe/downloadc78e658907e21112946b23471e0ee73fMD57iec/28822022-10-21 00:34:46.459oai:patua.iec.gov.br:iec/2882https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:34:46Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falseVG9kb3Mgb3MgZG9jdW1lbnRvcyBkZXNzYSBjb2xlw6fDo28gc2VndWVtIGEgTGljZW7Dp2EgQ3JlYXRpdmUgY29tbW9ucy4= |
dc.title.pt_BR.fl_str_mv |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
title |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
spellingShingle |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations Siqueira, Andrei Santos Antivirais / farmacologia Proteínas de Bactérias / farmacologia Proteínas de Transporte / farmacologia Cianobactérias / química Dengue / terapia Vírus da Dengue / efeitos de drogas Lectinas / farmacologia Proteínas do Envelope Viral / metabolismo Mutação Puntual Ligação Proteica Simulação de Dinâmica Molecular Temperatura Ambiente |
title_short |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
title_full |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
title_fullStr |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
title_full_unstemmed |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
title_sort |
Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations |
author |
Siqueira, Andrei Santos |
author_facet |
Siqueira, Andrei Santos Lima, Alex Ranieri Jerônimo Souza, Rafael Conceição de Santos, Alberdan Silva Vianez Júnior, João Lídio da Silva Gonçalves Gonçalves, Evonnildo Costa |
author_role |
author |
author2 |
Lima, Alex Ranieri Jerônimo Souza, Rafael Conceição de Santos, Alberdan Silva Vianez Júnior, João Lídio da Silva Gonçalves Gonçalves, Evonnildo Costa |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Siqueira, Andrei Santos Lima, Alex Ranieri Jerônimo Souza, Rafael Conceição de Santos, Alberdan Silva Vianez Júnior, João Lídio da Silva Gonçalves Gonçalves, Evonnildo Costa |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Antivirais / farmacologia Proteínas de Bactérias / farmacologia Proteínas de Transporte / farmacologia Cianobactérias / química Dengue / terapia Vírus da Dengue / efeitos de drogas Lectinas / farmacologia Proteínas do Envelope Viral / metabolismo Mutação Puntual Ligação Proteica Simulação de Dinâmica Molecular Temperatura Ambiente |
topic |
Antivirais / farmacologia Proteínas de Bactérias / farmacologia Proteínas de Transporte / farmacologia Cianobactérias / química Dengue / terapia Vírus da Dengue / efeitos de drogas Lectinas / farmacologia Proteínas do Envelope Viral / metabolismo Mutação Puntual Ligação Proteica Simulação de Dinâmica Molecular Temperatura Ambiente |
description |
The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol). |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-11-24T18:56:15Z |
dc.date.available.fl_str_mv |
2017-11-24T18:56:15Z |
dc.date.issued.fl_str_mv |
2017 |
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 |
SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/2882 |
dc.identifier.issn.-.fl_str_mv |
0006-291X |
dc.identifier.doi.-.fl_str_mv |
10.1016/j.bbrc.2017.06.160 |
identifier_str_mv |
SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017. 0006-291X 10.1016/j.bbrc.2017.06.160 |
url |
https://patua.iec.gov.br/handle/iec/2882 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
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Instituto Evandro Chagas (IEC) |
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IEC |
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IEC |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
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