Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers

Detalhes bibliográficos
Autor(a) principal: Barkhordari, Farzaneh
Data de Publicação: 2022
Outros Autores: Rismani, Elham, Tabasinezhad, Maryam, Asgari, Saeme, Nematollahi, Leila, Talebkhan Garoosi, Yeganeh
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/206000
Resumo: The present study deals with the computational design and analysis of a novel fusion protein based on a single chain variable fragment that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) in breast cancer cells. Alpha luffin, a small ribosome inactivating protein (RIP), was attached to the anti-HER2 antibody fragment. I-TASSER modeling provided the full-length structure of the fusion protein. Molecular docking evaluated the molecular interactions of the complementarity-determining regions of designed fusion protein to HER2. Energy minimization and molecular dynamics simulations were conducted to refine the complexes. RMSD plot revealed reasonable stability of the fusion protein during the simulation. The free binding energy profile of complexes affirmed a favorable binding affinity of proteins in complex with HER2 using molecular mechanics Poisson-Boltzmann surface area (G-MMPBSA) algorithm. In general, this approach looks promising in the development of new fusion proteins in terms of immunotoxins with appropriate cytotoxicity.
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spelling Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancersCancer Targeted therapyFusion proteinMolecular dynamics ImmunotoxinThe present study deals with the computational design and analysis of a novel fusion protein based on a single chain variable fragment that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) in breast cancer cells. Alpha luffin, a small ribosome inactivating protein (RIP), was attached to the anti-HER2 antibody fragment. I-TASSER modeling provided the full-length structure of the fusion protein. Molecular docking evaluated the molecular interactions of the complementarity-determining regions of designed fusion protein to HER2. Energy minimization and molecular dynamics simulations were conducted to refine the complexes. RMSD plot revealed reasonable stability of the fusion protein during the simulation. The free binding energy profile of complexes affirmed a favorable binding affinity of proteins in complex with HER2 using molecular mechanics Poisson-Boltzmann surface area (G-MMPBSA) algorithm. In general, this approach looks promising in the development of new fusion proteins in terms of immunotoxins with appropriate cytotoxicity.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2022-12-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/20600010.1590/s2175-97902022e20527Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/206000/197288Copyright (c) 2022 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessBarkhordari, FarzanehRismani, ElhamTabasinezhad, Maryam Asgari, SaemeNematollahi, LeilaTalebkhan Garoosi, Yeganeh2023-08-23T14:32:51Zoai:revistas.usp.br:article/206000Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-08-23T14:32:51Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
title Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
spellingShingle Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
Barkhordari, Farzaneh
Cancer
Targeted therapy
Fusion protein
Molecular dynamics
Immunotoxin
title_short Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
title_full Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
title_fullStr Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
title_full_unstemmed Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
title_sort Computational analysis of fusion protein of anti-HER2 scFv and alpha luffin: A new immunotoxin protein for HER2 positive cancers
author Barkhordari, Farzaneh
author_facet Barkhordari, Farzaneh
Rismani, Elham
Tabasinezhad, Maryam
Asgari, Saeme
Nematollahi, Leila
Talebkhan Garoosi, Yeganeh
author_role author
author2 Rismani, Elham
Tabasinezhad, Maryam
Asgari, Saeme
Nematollahi, Leila
Talebkhan Garoosi, Yeganeh
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Barkhordari, Farzaneh
Rismani, Elham
Tabasinezhad, Maryam
Asgari, Saeme
Nematollahi, Leila
Talebkhan Garoosi, Yeganeh
dc.subject.por.fl_str_mv Cancer
Targeted therapy
Fusion protein
Molecular dynamics
Immunotoxin
topic Cancer
Targeted therapy
Fusion protein
Molecular dynamics
Immunotoxin
description The present study deals with the computational design and analysis of a novel fusion protein based on a single chain variable fragment that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2) in breast cancer cells. Alpha luffin, a small ribosome inactivating protein (RIP), was attached to the anti-HER2 antibody fragment. I-TASSER modeling provided the full-length structure of the fusion protein. Molecular docking evaluated the molecular interactions of the complementarity-determining regions of designed fusion protein to HER2. Energy minimization and molecular dynamics simulations were conducted to refine the complexes. RMSD plot revealed reasonable stability of the fusion protein during the simulation. The free binding energy profile of complexes affirmed a favorable binding affinity of proteins in complex with HER2 using molecular mechanics Poisson-Boltzmann surface area (G-MMPBSA) algorithm. In general, this approach looks promising in the development of new fusion proteins in terms of immunotoxins with appropriate cytotoxicity.
publishDate 2022
dc.date.none.fl_str_mv 2022-12-23
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/206000
10.1590/s2175-97902022e20527
url https://www.revistas.usp.br/bjps/article/view/206000
identifier_str_mv 10.1590/s2175-97902022e20527
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/206000/197288
dc.rights.driver.fl_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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