Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach

Autores
Andujar, Sebastian Antonio; Tosso, Rodrigo David; Suvire, Fernando Daniel; Angelina, Emilio Luis; Peruchena, Nelida Maria; Cabedo, Nuria; Cortes, Diego; Enriz, Ricardo Daniel
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2−DR). A reduced 3D model for the binding pocket of the human D2−DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations. To obtain the different complexes of DA/D2−DR, we combined semiempirical (PM6), DFT (B3LYP/6-31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with the D2−DR was evaluated from potential energy surfaces and potential energy curves. A comparative study between the molecular flexibility of DA in the gas phase and at D2−DR was carried out. In addition, several molecular dynamics simulations were carried out to evaluate the molecular flexibility of the different complexes obtained. Our results allow us to postulate the complexes of type A as the ?biologically relevant conformations? of DA. In addition, the theoretical calculations reported here suggested that a mechanistic stepwise process takes place for DA in which the protonated nitrogen group (in any conformation) acts as the anchoring portion, and this process is followed by a rapid rearrangement of the conformation allowing the interaction of the catecholic OH groups.
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina
Fil: Cabedo, Nuria. Universidad de Valencia; España
Fil: Cortes, Diego. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Materia
dopamine
dopamine D2 receptor
molecular modeling
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:11336/268145
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/268145
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Searching the “Biologically Relevant”Conformation of Dopamine: A Computational ApproachAndujar, Sebastian AntonioTosso, Rodrigo DavidSuvire, Fernando DanielAngelina, Emilio LuisPeruchena, Nelida MariaCabedo, NuriaCortes, DiegoEnriz, Ricardo Danieldopaminedopamine D2 receptormolecular modelinghttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2−DR). A reduced 3D model for the binding pocket of the human D2−DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations. To obtain the different complexes of DA/D2−DR, we combined semiempirical (PM6), DFT (B3LYP/6-31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with the D2−DR was evaluated from potential energy surfaces and potential energy curves. A comparative study between the molecular flexibility of DA in the gas phase and at D2−DR was carried out. In addition, several molecular dynamics simulations were carried out to evaluate the molecular flexibility of the different complexes obtained. Our results allow us to postulate the complexes of type A as the ?biologically relevant conformations? of DA. In addition, the theoretical calculations reported here suggested that a mechanistic stepwise process takes place for DA in which the protonated nitrogen group (in any conformation) acts as the anchoring portion, and this process is followed by a rapid rearrangement of the conformation allowing the interaction of the catecholic OH groups.Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Cabedo, Nuria. Universidad de Valencia; EspañaFil: Cortes, Diego. Universidad de Valencia; EspañaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaAmerican Chemical Society2011-12info: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/11336/268145Andujar, Sebastian Antonio; Tosso, Rodrigo David; Suvire, Fernando Daniel; Angelina, Emilio Luis; Peruchena, Nelida Maria; et al.; Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach; American Chemical Society; Journal of Chemical Information and Modeling; 52; 1; 12-2011; 99-1121549-9596CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/ci2004225info:eu-repo/semantics/altIdentifier/doi/10.1021/ci2004225info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:03:08Zoai:ri.conicet.gov.ar:11336/268145instacron: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 10:03:08.798CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
title Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
spellingShingle Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
Andujar, Sebastian Antonio
dopamine
dopamine D2 receptor
molecular modeling
title_short Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
title_full Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
title_fullStr Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
title_full_unstemmed Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
title_sort Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach
dc.creator.none.fl_str_mv Andujar, Sebastian Antonio
Tosso, Rodrigo David
Suvire, Fernando Daniel
Angelina, Emilio Luis
Peruchena, Nelida Maria
Cabedo, Nuria
Cortes, Diego
Enriz, Ricardo Daniel
author Andujar, Sebastian Antonio
author_facet Andujar, Sebastian Antonio
Tosso, Rodrigo David
Suvire, Fernando Daniel
Angelina, Emilio Luis
Peruchena, Nelida Maria
Cabedo, Nuria
Cortes, Diego
Enriz, Ricardo Daniel
author_role author
author2 Tosso, Rodrigo David
Suvire, Fernando Daniel
Angelina, Emilio Luis
Peruchena, Nelida Maria
Cabedo, Nuria
Cortes, Diego
Enriz, Ricardo Daniel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv dopamine
dopamine D2 receptor
molecular modeling
topic dopamine
dopamine D2 receptor
molecular modeling
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2−DR). A reduced 3D model for the binding pocket of the human D2−DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations. To obtain the different complexes of DA/D2−DR, we combined semiempirical (PM6), DFT (B3LYP/6-31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with the D2−DR was evaluated from potential energy surfaces and potential energy curves. A comparative study between the molecular flexibility of DA in the gas phase and at D2−DR was carried out. In addition, several molecular dynamics simulations were carried out to evaluate the molecular flexibility of the different complexes obtained. Our results allow us to postulate the complexes of type A as the ?biologically relevant conformations? of DA. In addition, the theoretical calculations reported here suggested that a mechanistic stepwise process takes place for DA in which the protonated nitrogen group (in any conformation) acts as the anchoring portion, and this process is followed by a rapid rearrangement of the conformation allowing the interaction of the catecholic OH groups.
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Suvire, Fernando Daniel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Angelina, Emilio Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina
Fil: Cabedo, Nuria. Universidad de Valencia; España
Fil: Cortes, Diego. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
description We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2−DR). A reduced 3D model for the binding pocket of the human D2−DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations. To obtain the different complexes of DA/D2−DR, we combined semiempirical (PM6), DFT (B3LYP/6-31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with the D2−DR was evaluated from potential energy surfaces and potential energy curves. A comparative study between the molecular flexibility of DA in the gas phase and at D2−DR was carried out. In addition, several molecular dynamics simulations were carried out to evaluate the molecular flexibility of the different complexes obtained. Our results allow us to postulate the complexes of type A as the ?biologically relevant conformations? of DA. In addition, the theoretical calculations reported here suggested that a mechanistic stepwise process takes place for DA in which the protonated nitrogen group (in any conformation) acts as the anchoring portion, and this process is followed by a rapid rearrangement of the conformation allowing the interaction of the catecholic OH groups.
publishDate 2011
dc.date.none.fl_str_mv 2011-12
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/11336/268145
Andujar, Sebastian Antonio; Tosso, Rodrigo David; Suvire, Fernando Daniel; Angelina, Emilio Luis; Peruchena, Nelida Maria; et al.; Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach; American Chemical Society; Journal of Chemical Information and Modeling; 52; 1; 12-2011; 99-112
1549-9596
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268145
identifier_str_mv Andujar, Sebastian Antonio; Tosso, Rodrigo David; Suvire, Fernando Daniel; Angelina, Emilio Luis; Peruchena, Nelida Maria; et al.; Searching the “Biologically Relevant”Conformation of Dopamine: A Computational Approach; American Chemical Society; Journal of Chemical Information and Modeling; 52; 1; 12-2011; 99-112
1549-9596
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/ci2004225
info:eu-repo/semantics/altIdentifier/doi/10.1021/ci2004225
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 13.070432

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