In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy

Autores
Sierra Bello, Omar; Gonzalez, Janneth; Capani, Francisco; Barreto, George E.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder characterized mainly by a progressive loss of motor neurons. Glutamate excitotoxicity is likely the main cause of neuronal death, and Riluzole interferes with glutamate-mediated transmission. Thus, in such independent pathway, these effects may be partly due to inactivation of voltage-dependent sodium channels. Here we predict the structural model of the interaction and report the possible binding sites of Riluzole on Nav1.6 channel. The docked complexes were subjected to minimization and we further investigated the key interacting residues, binding free energies, pairing bridge determination, folding pattern, hydrogen bounding formation, hydrophobic contacts and flexibilities. Our results demonstrate that Riluzole interacts with the Nav1.6 channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799, suggesting possible cellular implications driven by these amino acids on Riluzole-Nav1.6 interaction, which may serve as an important output for a more specific and experimental drug design therapy against ALS. © 2012 Elsevier Ltd.
Fil: Sierra Bello, Omar. Pontificia Universidad Javeriana; Colombia
Fil: Gonzalez, Janneth. Pontificia Universidad Javeriana; Colombia
Fil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Barreto, George E.. Pontificia Universidad Javeriana; Colombia
Materia
Als
Gln 1799
Nav1.6
Riluzole
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:11336/67291
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/67291
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapySierra Bello, OmarGonzalez, JannethCapani, FranciscoBarreto, George E.AlsGln 1799Nav1.6Riluzolehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder characterized mainly by a progressive loss of motor neurons. Glutamate excitotoxicity is likely the main cause of neuronal death, and Riluzole interferes with glutamate-mediated transmission. Thus, in such independent pathway, these effects may be partly due to inactivation of voltage-dependent sodium channels. Here we predict the structural model of the interaction and report the possible binding sites of Riluzole on Nav1.6 channel. The docked complexes were subjected to minimization and we further investigated the key interacting residues, binding free energies, pairing bridge determination, folding pattern, hydrogen bounding formation, hydrophobic contacts and flexibilities. Our results demonstrate that Riluzole interacts with the Nav1.6 channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799, suggesting possible cellular implications driven by these amino acids on Riluzole-Nav1.6 interaction, which may serve as an important output for a more specific and experimental drug design therapy against ALS. © 2012 Elsevier Ltd.Fil: Sierra Bello, Omar. Pontificia Universidad Javeriana; ColombiaFil: Gonzalez, Janneth. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaAcademic Press Ltd - Elsevier Science Ltd2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67291Sierra Bello, Omar; Gonzalez, Janneth; Capani, Francisco; Barreto, George E.; In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy; Academic Press Ltd - Elsevier Science Ltd; Journal of Theoretical Biology; 315; 12-2012; 53-630022-5193CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jtbi.2012.09.004info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022519312004729info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:27:34Zoai:ri.conicet.gov.ar:11336/67291instacron: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 11:27:34.343CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
title In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
spellingShingle In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
Sierra Bello, Omar
Als
Gln 1799
Nav1.6
Riluzole
title_short In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
title_full In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
title_fullStr In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
title_full_unstemmed In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
title_sort In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy
dc.creator.none.fl_str_mv Sierra Bello, Omar
Gonzalez, Janneth
Capani, Francisco
Barreto, George E.
author Sierra Bello, Omar
author_facet Sierra Bello, Omar
Gonzalez, Janneth
Capani, Francisco
Barreto, George E.
author_role author
author2 Gonzalez, Janneth
Capani, Francisco
Barreto, George E.
author2_role author
author
author
dc.subject.none.fl_str_mv Als
Gln 1799
Nav1.6
Riluzole
topic Als
Gln 1799
Nav1.6
Riluzole
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder characterized mainly by a progressive loss of motor neurons. Glutamate excitotoxicity is likely the main cause of neuronal death, and Riluzole interferes with glutamate-mediated transmission. Thus, in such independent pathway, these effects may be partly due to inactivation of voltage-dependent sodium channels. Here we predict the structural model of the interaction and report the possible binding sites of Riluzole on Nav1.6 channel. The docked complexes were subjected to minimization and we further investigated the key interacting residues, binding free energies, pairing bridge determination, folding pattern, hydrogen bounding formation, hydrophobic contacts and flexibilities. Our results demonstrate that Riluzole interacts with the Nav1.6 channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799, suggesting possible cellular implications driven by these amino acids on Riluzole-Nav1.6 interaction, which may serve as an important output for a more specific and experimental drug design therapy against ALS. © 2012 Elsevier Ltd.
Fil: Sierra Bello, Omar. Pontificia Universidad Javeriana; Colombia
Fil: Gonzalez, Janneth. Pontificia Universidad Javeriana; Colombia
Fil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina
Fil: Barreto, George E.. Pontificia Universidad Javeriana; Colombia
description Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder characterized mainly by a progressive loss of motor neurons. Glutamate excitotoxicity is likely the main cause of neuronal death, and Riluzole interferes with glutamate-mediated transmission. Thus, in such independent pathway, these effects may be partly due to inactivation of voltage-dependent sodium channels. Here we predict the structural model of the interaction and report the possible binding sites of Riluzole on Nav1.6 channel. The docked complexes were subjected to minimization and we further investigated the key interacting residues, binding free energies, pairing bridge determination, folding pattern, hydrogen bounding formation, hydrophobic contacts and flexibilities. Our results demonstrate that Riluzole interacts with the Nav1.6 channel, more specifically in the key residues TYR 1787, LEU 1843 and GLN 1799, suggesting possible cellular implications driven by these amino acids on Riluzole-Nav1.6 interaction, which may serve as an important output for a more specific and experimental drug design therapy against ALS. © 2012 Elsevier Ltd.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
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/11336/67291
Sierra Bello, Omar; Gonzalez, Janneth; Capani, Francisco; Barreto, George E.; In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy; Academic Press Ltd - Elsevier Science Ltd; Journal of Theoretical Biology; 315; 12-2012; 53-63
0022-5193
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67291
identifier_str_mv Sierra Bello, Omar; Gonzalez, Janneth; Capani, Francisco; Barreto, George E.; In silico docking reveals possible Riluzole binding sites on Nav1.6 sodium channel: Implications for amyotrophic lateral sclerosis therapy; Academic Press Ltd - Elsevier Science Ltd; Journal of Theoretical Biology; 315; 12-2012; 53-63
0022-5193
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jtbi.2012.09.004
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022519312004729
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
dc.publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
publisher.none.fl_str_mv Academic Press Ltd - Elsevier Science Ltd
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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