Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1021/acs.jcim.9b00911 http://hdl.handle.net/11449/198341 |
Resumo: | Rational design of proteins via mutagenesis is crucial for several biotechnological applications. A significant challenge of the computational strategies used to predict optimized mutations is to understand the influence of each amino acid during the folding process. In the present work, chymotrypsin inhibitor 2 (CI2) and several of its designed mutants have been simulated using a non-native hydrophobic and electrostatic potential as a structure-based Cα model. Through these simulations, we could identify the most critical folding stage to accelerate CI2 and also the charged residues responsible for providing its thermostability. The replacement of ionizable residues for hydrophobic ones tended to promote the formation of the CI2 secondary structure in the early transition state, which speeds up folding. However, this same replacement destabilized the native structure, and there was a decrease in the protein thermostability. Such a simple method proved to be capable of providing valuable information about thermodynamics and kinetics of CI2 and its mutations, thus being a fast alternative to the study of rational protein design. |
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Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native InteractionsRational design of proteins via mutagenesis is crucial for several biotechnological applications. A significant challenge of the computational strategies used to predict optimized mutations is to understand the influence of each amino acid during the folding process. In the present work, chymotrypsin inhibitor 2 (CI2) and several of its designed mutants have been simulated using a non-native hydrophobic and electrostatic potential as a structure-based Cα model. Through these simulations, we could identify the most critical folding stage to accelerate CI2 and also the charged residues responsible for providing its thermostability. The replacement of ionizable residues for hydrophobic ones tended to promote the formation of the CI2 secondary structure in the early transition state, which speeds up folding. However, this same replacement destabilized the native structure, and there was a decrease in the protein thermostability. Such a simple method proved to be capable of providing valuable information about thermodynamics and kinetics of CI2 and its mutations, thus being a fast alternative to the study of rational protein design.Department of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)Brazilian Biosciences National Laboratory Brazilian Center for Research in Energy and Materials LNBio/CNPEMBrazilian Biorenewables National Laboratory LNBR Brazilian Center for Research in Energy and Materials CNPEMCenter for Theoretical Biological Physics Rice UniversityDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)LNBio/CNPEMCNPEMRice UniversityB. Da Silva, Fernando [UNESP]M. De Oliveira, ViníciusSanches, Murilo N. [UNESP]Contessoto, Vinícius G.Leite, Vitor B. P. [UNESP]2020-12-12T01:10:09Z2020-12-12T01:10:09Z2020-02-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article982-988http://dx.doi.org/10.1021/acs.jcim.9b00911Journal of Chemical Information and Modeling, v. 60, n. 2, p. 982-988, 2020.1520-51421549-9596http://hdl.handle.net/11449/19834110.1021/acs.jcim.9b009112-s2.0-85077220845Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Chemical Information and Modelinginfo:eu-repo/semantics/openAccess2021-10-23T10:11:17Zoai:repositorio.unesp.br:11449/198341Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T10:11:17Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
title |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
spellingShingle |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions B. Da Silva, Fernando [UNESP] |
title_short |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
title_full |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
title_fullStr |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
title_full_unstemmed |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
title_sort |
Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions |
author |
B. Da Silva, Fernando [UNESP] |
author_facet |
B. Da Silva, Fernando [UNESP] M. De Oliveira, Vinícius Sanches, Murilo N. [UNESP] Contessoto, Vinícius G. Leite, Vitor B. P. [UNESP] |
author_role |
author |
author2 |
M. De Oliveira, Vinícius Sanches, Murilo N. [UNESP] Contessoto, Vinícius G. Leite, Vitor B. P. [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) LNBio/CNPEM CNPEM Rice University |
dc.contributor.author.fl_str_mv |
B. Da Silva, Fernando [UNESP] M. De Oliveira, Vinícius Sanches, Murilo N. [UNESP] Contessoto, Vinícius G. Leite, Vitor B. P. [UNESP] |
description |
Rational design of proteins via mutagenesis is crucial for several biotechnological applications. A significant challenge of the computational strategies used to predict optimized mutations is to understand the influence of each amino acid during the folding process. In the present work, chymotrypsin inhibitor 2 (CI2) and several of its designed mutants have been simulated using a non-native hydrophobic and electrostatic potential as a structure-based Cα model. Through these simulations, we could identify the most critical folding stage to accelerate CI2 and also the charged residues responsible for providing its thermostability. The replacement of ionizable residues for hydrophobic ones tended to promote the formation of the CI2 secondary structure in the early transition state, which speeds up folding. However, this same replacement destabilized the native structure, and there was a decrease in the protein thermostability. Such a simple method proved to be capable of providing valuable information about thermodynamics and kinetics of CI2 and its mutations, thus being a fast alternative to the study of rational protein design. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T01:10:09Z 2020-12-12T01:10:09Z 2020-02-24 |
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.uri.fl_str_mv |
http://dx.doi.org/10.1021/acs.jcim.9b00911 Journal of Chemical Information and Modeling, v. 60, n. 2, p. 982-988, 2020. 1520-5142 1549-9596 http://hdl.handle.net/11449/198341 10.1021/acs.jcim.9b00911 2-s2.0-85077220845 |
url |
http://dx.doi.org/10.1021/acs.jcim.9b00911 http://hdl.handle.net/11449/198341 |
identifier_str_mv |
Journal of Chemical Information and Modeling, v. 60, n. 2, p. 982-988, 2020. 1520-5142 1549-9596 10.1021/acs.jcim.9b00911 2-s2.0-85077220845 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Chemical Information and Modeling |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
982-988 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803047383325474816 |