Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study

Autores
Baler, K.; Martín, Osvaldo Antonio; Carignano, Marcelo A.; Ameer, G. A.; Vila, Jorge Alberto; Szleifer, Igal
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A better understanding of protein aggregation is bound to translate into
critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
Fil: Baler, K.. Northwestern University; Estados Unidos
Fil: Martín, Osvaldo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina
Fil: Carignano, Marcelo A.. Northwestern University; Estados Unidos
Fil: Ameer, G. A.. Northwestern University; Estados Unidos
Fil: Vila, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina
Fil: Szleifer, Igal. Northwestern University; Estados Unidos
Materia
Albumin
Electrostatic
Ph
Molecular Dynamics
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/31294
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/31294
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics StudyBaler, K.Martín, Osvaldo AntonioCarignano, Marcelo A.Ameer, G. A.Vila, Jorge AlbertoSzleifer, IgalAlbuminElectrostaticPhMolecular Dynamicshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A better understanding of protein aggregation is bound to translate into<br />critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.Fil: Baler, K.. Northwestern University; Estados UnidosFil: Martín, Osvaldo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; ArgentinaFil: Carignano, Marcelo A.. Northwestern University; Estados UnidosFil: Ameer, G. A.. Northwestern University; Estados UnidosFil: Vila, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; ArgentinaFil: Szleifer, Igal. Northwestern University; Estados UnidosAmerican Chemical Society2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31294Szleifer, Igal; Vila, Jorge Alberto; Ameer, G. A.; Carignano, Marcelo A.; Martín, Osvaldo Antonio; Baler, K.; et al.; Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study; American Chemical Society; Journal of Physical Chemistry B; 118; 4; 1-2014; 921-9301520-6106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jp409936vinfo:eu-repo/semantics/altIdentifier/doi/10.1021/jp409936vinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:03:15Zoai:ri.conicet.gov.ar:11336/31294instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:03:16.133CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
title Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
spellingShingle Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
Baler, K.
Albumin
Electrostatic
Ph
Molecular Dynamics
title_short Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
title_full Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
title_fullStr Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
title_full_unstemmed Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
title_sort Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study
dc.creator.none.fl_str_mv Baler, K.
Martín, Osvaldo Antonio
Carignano, Marcelo A.
Ameer, G. A.
Vila, Jorge Alberto
Szleifer, Igal
author Baler, K.
author_facet Baler, K.
Martín, Osvaldo Antonio
Carignano, Marcelo A.
Ameer, G. A.
Vila, Jorge Alberto
Szleifer, Igal
author_role author
author2 Martín, Osvaldo Antonio
Carignano, Marcelo A.
Ameer, G. A.
Vila, Jorge Alberto
Szleifer, Igal
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Albumin
Electrostatic
Ph
Molecular Dynamics
topic Albumin
Electrostatic
Ph
Molecular Dynamics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A better understanding of protein aggregation is bound to translate into<br />critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
Fil: Baler, K.. Northwestern University; Estados Unidos
Fil: Martín, Osvaldo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina
Fil: Carignano, Marcelo A.. Northwestern University; Estados Unidos
Fil: Ameer, G. A.. Northwestern University; Estados Unidos
Fil: Vila, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis ; Argentina
Fil: Szleifer, Igal. Northwestern University; Estados Unidos
description A better understanding of protein aggregation is bound to translate into<br />critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/31294
Szleifer, Igal; Vila, Jorge Alberto; Ameer, G. A.; Carignano, Marcelo A.; Martín, Osvaldo Antonio; Baler, K.; et al.; Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study; American Chemical Society; Journal of Physical Chemistry B; 118; 4; 1-2014; 921-930
1520-6106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31294
identifier_str_mv Szleifer, Igal; Vila, Jorge Alberto; Ameer, G. A.; Carignano, Marcelo A.; Martín, Osvaldo Antonio; Baler, K.; et al.; Electrostatic Unfolding and Interactions of Albumin Driven by pH Changes: A Molecular Dynamics Study; American Chemical Society; Journal of Physical Chemistry B; 118; 4; 1-2014; 921-930
1520-6106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/jp409936v
info:eu-repo/semantics/altIdentifier/doi/10.1021/jp409936v
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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