Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site

Autores
Gastaldi, María Salomé; Felsztyna, Iván; Sánchez, Mariela Eugenia; Garcia, Daniel Asmed; Miguel, Virginia
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
TThe insect GABA A receptor (RDL) is an important protein target for natural and artificial insecticides that act by blocking the channel and inhibiting the ions flux through it. We aim ıto characterize the non-competitive antagonists II (NCA-II) binding site, to develop tools that allow us to obtain new insecticidal compounds that share this same blocking site. This site is targeted by isoxazolines, being Fluralaner a canonical representative of this chemical class. We pretend to evaluate whether these compounds could interact with the membrane where the receptor is embedded and module it. Different 3D models of the Aedes aegypti homopentamer RDL were developed in our group by homology modelling, due to the fact that there is no available crystallographic structure of the receptor. Distinct templates corresponding to different conformational states of the channel were used. We have evaluated the performance of the models by molecular docking assays of Fluralaner, in order to determine which of them is capable of replicating the Fluralaner binding pose. The model obtained from the 3RHW template (PDB ID 3RHW), which has an open channel conformation, was the one that best replicated both the interactions reported by biochemical assays, as well as the spatial orientation of the Fluralaner molecule at the receptor blocking site. These molecular docking assays of the Fluralaner at the NCA-II site allowed us to select a model of the Aedes aegypti GABAA receptor that reproduces that reported by previous works. We performed ALL ATOM detail Molecular Dynamics simulations to characterize the membrane-receptor-ligand interactions, which allowed us to validate the selected model since the interactions between the Fluranaler and the rest of the system components were as expected.
Fil: Gastaldi, María Salomé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Sánchez, Mariela Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
XLIX Reunión Anual Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
Materia
INSECTICIDE
GABAA RECEPTOR
DOCKING
FLURALANER
BINDING SITE
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:11336/189158
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/189158
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Gabaergic insecticides exploration: Characterization of one GABAA receptor binding siteGastaldi, María SaloméFelsztyna, IvánSánchez, Mariela EugeniaGarcia, Daniel AsmedMiguel, VirginiaINSECTICIDEGABAA RECEPTORDOCKINGFLURALANERBINDING SITEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1TThe insect GABA A receptor (RDL) is an important protein target for natural and artificial insecticides that act by blocking the channel and inhibiting the ions flux through it. We aim ıto characterize the non-competitive antagonists II (NCA-II) binding site, to develop tools that allow us to obtain new insecticidal compounds that share this same blocking site. This site is targeted by isoxazolines, being Fluralaner a canonical representative of this chemical class. We pretend to evaluate whether these compounds could interact with the membrane where the receptor is embedded and module it. Different 3D models of the Aedes aegypti homopentamer RDL were developed in our group by homology modelling, due to the fact that there is no available crystallographic structure of the receptor. Distinct templates corresponding to different conformational states of the channel were used. We have evaluated the performance of the models by molecular docking assays of Fluralaner, in order to determine which of them is capable of replicating the Fluralaner binding pose. The model obtained from the 3RHW template (PDB ID 3RHW), which has an open channel conformation, was the one that best replicated both the interactions reported by biochemical assays, as well as the spatial orientation of the Fluralaner molecule at the receptor blocking site. These molecular docking assays of the Fluralaner at the NCA-II site allowed us to select a model of the Aedes aegypti GABAA receptor that reproduces that reported by previous works. We performed ALL ATOM detail Molecular Dynamics simulations to characterize the membrane-receptor-ligand interactions, which allowed us to validate the selected model since the interactions between the Fluranaler and the rest of the system components were as expected.Fil: Gastaldi, María Salomé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFil: Sánchez, Mariela Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaFil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; ArgentinaXLIX Reunión Anual Sociedad Argentina de BiofísicaBuenos AiresArgentinaSociedad Argentina de BiofísicaSociedad Argentina de BiofísicaDelfino, Jose MariaCelej, Maria SoledadMangialavori, Irene Cecilia2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/189158Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site; XLIX Reunión Anual Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 88-88978-987-27591-9-3CONICET DigitalCONICETenginfo: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 Técnicas2025-09-10T13:25:06Zoai:ri.conicet.gov.ar:11336/189158instacron: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:34982025-09-10 13:25:06.616CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
title Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
spellingShingle Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
Gastaldi, María Salomé
INSECTICIDE
GABAA RECEPTOR
DOCKING
FLURALANER
BINDING SITE
title_short Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
title_full Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
title_fullStr Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
title_full_unstemmed Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
title_sort Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site
dc.creator.none.fl_str_mv Gastaldi, María Salomé
Felsztyna, Iván
Sánchez, Mariela Eugenia
Garcia, Daniel Asmed
Miguel, Virginia
author Gastaldi, María Salomé
author_facet Gastaldi, María Salomé
Felsztyna, Iván
Sánchez, Mariela Eugenia
Garcia, Daniel Asmed
Miguel, Virginia
author_role author
author2 Felsztyna, Iván
Sánchez, Mariela Eugenia
Garcia, Daniel Asmed
Miguel, Virginia
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Delfino, Jose Maria
Celej, Maria Soledad
Mangialavori, Irene Cecilia
dc.subject.none.fl_str_mv INSECTICIDE
GABAA RECEPTOR
DOCKING
FLURALANER
BINDING SITE
topic INSECTICIDE
GABAA RECEPTOR
DOCKING
FLURALANER
BINDING SITE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv TThe insect GABA A receptor (RDL) is an important protein target for natural and artificial insecticides that act by blocking the channel and inhibiting the ions flux through it. We aim ıto characterize the non-competitive antagonists II (NCA-II) binding site, to develop tools that allow us to obtain new insecticidal compounds that share this same blocking site. This site is targeted by isoxazolines, being Fluralaner a canonical representative of this chemical class. We pretend to evaluate whether these compounds could interact with the membrane where the receptor is embedded and module it. Different 3D models of the Aedes aegypti homopentamer RDL were developed in our group by homology modelling, due to the fact that there is no available crystallographic structure of the receptor. Distinct templates corresponding to different conformational states of the channel were used. We have evaluated the performance of the models by molecular docking assays of Fluralaner, in order to determine which of them is capable of replicating the Fluralaner binding pose. The model obtained from the 3RHW template (PDB ID 3RHW), which has an open channel conformation, was the one that best replicated both the interactions reported by biochemical assays, as well as the spatial orientation of the Fluralaner molecule at the receptor blocking site. These molecular docking assays of the Fluralaner at the NCA-II site allowed us to select a model of the Aedes aegypti GABAA receptor that reproduces that reported by previous works. We performed ALL ATOM detail Molecular Dynamics simulations to characterize the membrane-receptor-ligand interactions, which allowed us to validate the selected model since the interactions between the Fluranaler and the rest of the system components were as expected.
Fil: Gastaldi, María Salomé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Sánchez, Mariela Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
Fil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Química. Cátedra de Química Biológica; Argentina
XLIX Reunión Anual Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
description TThe insect GABA A receptor (RDL) is an important protein target for natural and artificial insecticides that act by blocking the channel and inhibiting the ions flux through it. We aim ıto characterize the non-competitive antagonists II (NCA-II) binding site, to develop tools that allow us to obtain new insecticidal compounds that share this same blocking site. This site is targeted by isoxazolines, being Fluralaner a canonical representative of this chemical class. We pretend to evaluate whether these compounds could interact with the membrane where the receptor is embedded and module it. Different 3D models of the Aedes aegypti homopentamer RDL were developed in our group by homology modelling, due to the fact that there is no available crystallographic structure of the receptor. Distinct templates corresponding to different conformational states of the channel were used. We have evaluated the performance of the models by molecular docking assays of Fluralaner, in order to determine which of them is capable of replicating the Fluralaner binding pose. The model obtained from the 3RHW template (PDB ID 3RHW), which has an open channel conformation, was the one that best replicated both the interactions reported by biochemical assays, as well as the spatial orientation of the Fluralaner molecule at the receptor blocking site. These molecular docking assays of the Fluralaner at the NCA-II site allowed us to select a model of the Aedes aegypti GABAA receptor that reproduces that reported by previous works. We performed ALL ATOM detail Molecular Dynamics simulations to characterize the membrane-receptor-ligand interactions, which allowed us to validate the selected model since the interactions between the Fluranaler and the rest of the system components were as expected.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/11336/189158
Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site; XLIX Reunión Anual Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 88-88
978-987-27591-9-3
CONICET Digital
CONICET
url http://hdl.handle.net/11336/189158
identifier_str_mv Gabaergic insecticides exploration: Characterization of one GABAA receptor binding site; XLIX Reunión Anual Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 88-88
978-987-27591-9-3
CONICET Digital
CONICET
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language eng
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dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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