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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/66696
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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 Técnicas2025-09-29T09:55:15Zoai: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:34982025-09-29 09:55:15.639CONICET 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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1844613667610427392 |
score |
13.070432 |