A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor

Autores
Obiol, Diego Javier; Amundarain, María Julia; Jaure, Omar David Argentino; Zamarreño, Fernando; Antollini, Silvia Susana; Costabel, M.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Free fatty acids (FFAs) are important cellular components that increase under certainpathological conditions. One of the effects of FFAs is a protection mechanism through themodulation of ion channels. The activity of the nicotinic acetylcholine receptor (nAchR) isblocked by certain FFAs and its binding site is located at the lipid-protein interface. Theobjective of this work was to determine, by means of molecular dynamics (MD), thepossible points of contact and the effect produced by five different FFAs, located inannular and non-annular sites. The study was carried out on a system composed by amodel of AChR from Torpedo marmorata (PDB ID: 2BG9) that was elaborated from PDBID: 4COF as a template because the e-values were the lowest for each subunit andbecause it represented the closed desensitized state. The evaluation of thestereochemical parameters for the refined model was improved with respect to 2BG9.The refined model was incorporated into a lipid bilayer composed with a ratio of 1:1:3 ofcholesterol, POPA and POPC respectively. We replaced three phospholipids from the lipidbilayer with three of the corresponding free fatty acids: cis-18:1ω-6, cis-18:1ω-9,cis-18:1ω-11, cis-18:1ω-13 and trans-18:1ω-9 in annular or non-annular areas. From theMD runs we obtained the most statistically relevant conformations of each FFAs in eachof the systems, we determined the possible contacts with residues of the nAChR and theresulting profile of pore radius. In general, the results show that more contacts areestablished when FFAs are located in non-annular regions. As expected, contacts areestablished in a much greater proportion with non-polar residues. cis-18:1ω-11 in nonannular sites leads to conformations that open the pore of the channel, while in annularsites it stabilizes the desensitized state. With cis-18:1ω-13 a similar behavior isobserved, although in non-annular sites it produces a pronounced constriction in theextracellular domain.
Fil: Obiol, Diego Javier. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Amundarain, María Julia. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Jaure, Omar David Argentino. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Costabel, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica
San Luis
Argentina
Sociedad Argentina de Biofísica
Materia
nicotinic acetylcholine receptor
free fatty acids
molecular dynamic
lipid bilayer
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:11336/153805
Acceder
id CONICETDig_2bc31e3f8e05f781f53cb948b9d02c33
oai_identifier_str oai:ri.conicet.gov.ar:11336/153805
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptorObiol, Diego JavierAmundarain, María JuliaJaure, Omar David ArgentinoZamarreño, FernandoAntollini, Silvia SusanaCostabel, M.nicotinic acetylcholine receptorfree fatty acidsmolecular dynamiclipid bilayerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Free fatty acids (FFAs) are important cellular components that increase under certainpathological conditions. One of the effects of FFAs is a protection mechanism through themodulation of ion channels. The activity of the nicotinic acetylcholine receptor (nAchR) isblocked by certain FFAs and its binding site is located at the lipid-protein interface. Theobjective of this work was to determine, by means of molecular dynamics (MD), thepossible points of contact and the effect produced by five different FFAs, located inannular and non-annular sites. The study was carried out on a system composed by amodel of AChR from Torpedo marmorata (PDB ID: 2BG9) that was elaborated from PDBID: 4COF as a template because the e-values were the lowest for each subunit andbecause it represented the closed desensitized state. The evaluation of thestereochemical parameters for the refined model was improved with respect to 2BG9.The refined model was incorporated into a lipid bilayer composed with a ratio of 1:1:3 ofcholesterol, POPA and POPC respectively. We replaced three phospholipids from the lipidbilayer with three of the corresponding free fatty acids: cis-18:1ω-6, cis-18:1ω-9,cis-18:1ω-11, cis-18:1ω-13 and trans-18:1ω-9 in annular or non-annular areas. From theMD runs we obtained the most statistically relevant conformations of each FFAs in eachof the systems, we determined the possible contacts with residues of the nAChR and theresulting profile of pore radius. In general, the results show that more contacts areestablished when FFAs are located in non-annular regions. As expected, contacts areestablished in a much greater proportion with non-polar residues. cis-18:1ω-11 in nonannular sites leads to conformations that open the pore of the channel, while in annularsites it stabilizes the desensitized state. With cis-18:1ω-13 a similar behavior isobserved, although in non-annular sites it produces a pronounced constriction in theextracellular domain.Fil: Obiol, Diego Javier. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Amundarain, María Julia. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Jaure, Omar David Argentino. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Costabel, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaXLVIII Reunión Anual de la Sociedad Argentina de BiofísicaSan LuisArgentinaSociedad Argentina de BiofísicaSociedad Argentina de BiofísicaAndujar, Sebastian Antonio2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/153805A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 1-4978-987-27591-7-9CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.arinfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:47Zoai:ri.conicet.gov.ar:11336/153805instacron: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 09:35:48.104CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
title A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
spellingShingle A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
Obiol, Diego Javier
nicotinic acetylcholine receptor
free fatty acids
molecular dynamic
lipid bilayer
title_short A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
title_full A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
title_fullStr A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
title_full_unstemmed A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
title_sort A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor
dc.creator.none.fl_str_mv Obiol, Diego Javier
Amundarain, María Julia
Jaure, Omar David Argentino
Zamarreño, Fernando
Antollini, Silvia Susana
Costabel, M.
author Obiol, Diego Javier
author_facet Obiol, Diego Javier
Amundarain, María Julia
Jaure, Omar David Argentino
Zamarreño, Fernando
Antollini, Silvia Susana
Costabel, M.
author_role author
author2 Amundarain, María Julia
Jaure, Omar David Argentino
Zamarreño, Fernando
Antollini, Silvia Susana
Costabel, M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Andujar, Sebastian Antonio
dc.subject.none.fl_str_mv nicotinic acetylcholine receptor
free fatty acids
molecular dynamic
lipid bilayer
topic nicotinic acetylcholine receptor
free fatty acids
molecular dynamic
lipid bilayer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Free fatty acids (FFAs) are important cellular components that increase under certainpathological conditions. One of the effects of FFAs is a protection mechanism through themodulation of ion channels. The activity of the nicotinic acetylcholine receptor (nAchR) isblocked by certain FFAs and its binding site is located at the lipid-protein interface. Theobjective of this work was to determine, by means of molecular dynamics (MD), thepossible points of contact and the effect produced by five different FFAs, located inannular and non-annular sites. The study was carried out on a system composed by amodel of AChR from Torpedo marmorata (PDB ID: 2BG9) that was elaborated from PDBID: 4COF as a template because the e-values were the lowest for each subunit andbecause it represented the closed desensitized state. The evaluation of thestereochemical parameters for the refined model was improved with respect to 2BG9.The refined model was incorporated into a lipid bilayer composed with a ratio of 1:1:3 ofcholesterol, POPA and POPC respectively. We replaced three phospholipids from the lipidbilayer with three of the corresponding free fatty acids: cis-18:1ω-6, cis-18:1ω-9,cis-18:1ω-11, cis-18:1ω-13 and trans-18:1ω-9 in annular or non-annular areas. From theMD runs we obtained the most statistically relevant conformations of each FFAs in eachof the systems, we determined the possible contacts with residues of the nAChR and theresulting profile of pore radius. In general, the results show that more contacts areestablished when FFAs are located in non-annular regions. As expected, contacts areestablished in a much greater proportion with non-polar residues. cis-18:1ω-11 in nonannular sites leads to conformations that open the pore of the channel, while in annularsites it stabilizes the desensitized state. With cis-18:1ω-13 a similar behavior isobserved, although in non-annular sites it produces a pronounced constriction in theextracellular domain.
Fil: Obiol, Diego Javier. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Amundarain, María Julia. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Jaure, Omar David Argentino. Universidad Nacional del Sur. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Costabel, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica
San Luis
Argentina
Sociedad Argentina de Biofísica
description Free fatty acids (FFAs) are important cellular components that increase under certainpathological conditions. One of the effects of FFAs is a protection mechanism through themodulation of ion channels. The activity of the nicotinic acetylcholine receptor (nAchR) isblocked by certain FFAs and its binding site is located at the lipid-protein interface. Theobjective of this work was to determine, by means of molecular dynamics (MD), thepossible points of contact and the effect produced by five different FFAs, located inannular and non-annular sites. The study was carried out on a system composed by amodel of AChR from Torpedo marmorata (PDB ID: 2BG9) that was elaborated from PDBID: 4COF as a template because the e-values were the lowest for each subunit andbecause it represented the closed desensitized state. The evaluation of thestereochemical parameters for the refined model was improved with respect to 2BG9.The refined model was incorporated into a lipid bilayer composed with a ratio of 1:1:3 ofcholesterol, POPA and POPC respectively. We replaced three phospholipids from the lipidbilayer with three of the corresponding free fatty acids: cis-18:1ω-6, cis-18:1ω-9,cis-18:1ω-11, cis-18:1ω-13 and trans-18:1ω-9 in annular or non-annular areas. From theMD runs we obtained the most statistically relevant conformations of each FFAs in eachof the systems, we determined the possible contacts with residues of the nAChR and theresulting profile of pore radius. In general, the results show that more contacts areestablished when FFAs are located in non-annular regions. As expected, contacts areestablished in a much greater proportion with non-polar residues. cis-18:1ω-11 in nonannular sites leads to conformations that open the pore of the channel, while in annularsites it stabilizes the desensitized state. With cis-18:1ω-13 a similar behavior isobserved, although in non-annular sites it produces a pronounced constriction in theextracellular domain.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/153805
A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 1-4
978-987-27591-7-9
CONICET Digital
CONICET
url http://hdl.handle.net/11336/153805
identifier_str_mv A Molecular Dynamic approach to the differential interaction between unsaturated free fatty acids and the nicotinic acetylcholine receptor; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 1-4
978-987-27591-7-9
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
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/
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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