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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/31294
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:35:14Zoai: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:34982025-09-29 09:35:14.269CONICET 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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1844613095426621440 |
score |
13.070432 |