Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins

Autores
Vorobjev, Yury N.; Scheraga, Harold A.; Vila, Jorge Alberto
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.
Fil: Vorobjev, Yury N.. Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Science; Rusia. Novosibirsk State University; Rusia. Cornell University; Estados Unidos
Fil: Scheraga, Harold A.. Cornell 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 "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina
Materia
Continuum Dielectric Model
Molecular Dynamics
Pka-Predictions
Protein Ionization
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:11336/66696
Acceder
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spelling Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteinsVorobjev, Yury N.Scheraga, Harold A.Vila, Jorge AlbertoContinuum Dielectric ModelMolecular DynamicsPka-PredictionsProtein Ionizationhttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.Fil: Vorobjev, Yury N.. Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Science; Rusia. Novosibirsk State University; Rusia. Cornell University; Estados UnidosFil: Scheraga, Harold A.. Cornell 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 "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaAdenine Press2018-02-24info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66696Vorobjev, Yury N.; Scheraga, Harold A.; Vila, Jorge Alberto; Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins; Adenine Press; Journal Of Biomolecular Structure & Dynamics; 36; 3; 24-2-2018; 561-5740739-1102CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1080/07391102.2017.1288169info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.1080/07391102.2017.1288169info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:24:21Zoai:ri.conicet.gov.ar:11336/66696instacron: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 11:24:21.928CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
title Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
spellingShingle Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
Vorobjev, Yury N.
Continuum Dielectric Model
Molecular Dynamics
Pka-Predictions
Protein Ionization
title_short Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
title_full Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
title_fullStr Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
title_full_unstemmed Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
title_sort Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins
dc.creator.none.fl_str_mv Vorobjev, Yury N.
Scheraga, Harold A.
Vila, Jorge Alberto
author Vorobjev, Yury N.
author_facet Vorobjev, Yury N.
Scheraga, Harold A.
Vila, Jorge Alberto
author_role author
author2 Scheraga, Harold A.
Vila, Jorge Alberto
author2_role author
author
dc.subject.none.fl_str_mv Continuum Dielectric Model
Molecular Dynamics
Pka-Predictions
Protein Ionization
topic Continuum Dielectric Model
Molecular Dynamics
Pka-Predictions
Protein Ionization
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.
Fil: Vorobjev, Yury N.. Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Science; Rusia. Novosibirsk State University; Rusia. Cornell University; Estados Unidos
Fil: Scheraga, Harold A.. Cornell 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 "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; Argentina
description A computational method, to predict the pKa values of the ionizable residues Asp, Glu, His, Tyr, and Lys of proteins, is presented here. Calculation of the electrostatic free-energy of the proteins is based on an efficient version of a continuum dielectric electrostatic model. The conformational flexibility of the protein is taken into account by carrying out molecular dynamics simulations of 10 ns in implicit water. The accuracy of the proposed method of calculation of pKa values is estimated from a test set of experimental pKa data for 297 ionizable residues from 34 proteins. The pKa-prediction test shows that, on average, 57, 86, and 95% of all predictions have an error lower than 0.5, 1.0, and 1.5 pKa units, respectively. This work contributes to our general understanding of the importance of protein flexibility for an accurate computation of pKa, providing critical insight about the significance of the multiple neutral states of acid and histidine residues for pKa-prediction, and may spur significant progress in our effort to develop a fast and accurate electrostatic-based method for pKa-predictions of proteins as a function of pH.
publishDate 2018
dc.date.none.fl_str_mv 2018-02-24
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/11336/66696
Vorobjev, Yury N.; Scheraga, Harold A.; Vila, Jorge Alberto; Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins; Adenine Press; Journal Of Biomolecular Structure & Dynamics; 36; 3; 24-2-2018; 561-574
0739-1102
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66696
identifier_str_mv Vorobjev, Yury N.; Scheraga, Harold A.; Vila, Jorge Alberto; Coupled molecular dynamics and continuum electrostatic method to compute the ionization pKa’s of proteins as a function of pH. Test on a large set of proteins; Adenine Press; Journal Of Biomolecular Structure & Dynamics; 36; 3; 24-2-2018; 561-574
0739-1102
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1080/07391102.2017.1288169
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.1080/07391102.2017.1288169
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
dc.publisher.none.fl_str_mv Adenine Press
publisher.none.fl_str_mv Adenine Press
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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