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dc.contributor.author
Felsztyna, Iván
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Gastaldi, María Salomé
dc.contributor.author
Villarreal, Marcos Ariel
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Garcia, Daniel Asmed
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Miguel, Virginia
dc.contributor.other
Delfino, Jose Maria
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Celej, Maria Soledad
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Ambroggio, Ernesto Esteban
dc.date.available
2024-02-26T13:52:33Z
dc.date.issued
2020
dc.identifier.citation
Assessment of insect GABAA receptor homology models performance for virtual screening and their validation by molecular dynamics simulations; Biofísica en tiempos de COVID-19 : Primeras Jornadas Virtuales SAB 2020; Buenos Aires; Argentina; 2020; 60-60
dc.identifier.isbn
978-987-27591-8-6
dc.identifier.uri
http://hdl.handle.net/11336/228411
dc.description.abstract
Insect nervous system is the main target for the most used insecticides, as is the case of GABAA receptor (GABAA-R) non-competitive antagonists (NCAs). In insects, the homopentamer formed by the Rdl subunit (Rdlhomo5) is the most representative type of GABAA-R. Rdlhomo5 presents several binding sites for NCAs. The NCA-IA site is located inside the channel pore and is targeted by polychlorocycloalkanes, cyclodienes and phenylpyrazoles. Also, a NCA-II site is located in the transmembrane domains interfaces and is targeted by fluralaner. Since there are no experimental 3D structures of any insect Rdlhomo5, in a previous work we performed homology modelling of Aedes aegypti Rdlhomo5 using templates in different pharmacological states. We aim to validate structural models suitable for performing virtual screening of new NCAs. We have now evaluated ten different Rdlhomo5 homology models by a retrospective virtual screening. A set of active ligands for the NCA-I site and a set of property-matched decoys were subjected to molecular docking. Virtual screening performance in these models was evaluated by the calculation of ROC curves and ligand enrichment factors. The model with the best performance was embedded in a POPC bilayer and subjected to ̴200 ns molecular dynamics simulations, both in the apo state and in complex with fipronil, a NCA-I site binder insecticide. The protein showed small RMSD values in both states, indicating the structure stability of the homology model. Also, the key interactions between fipronil and the Rdlhomo5 remained stable through the entire MD simulation time. We are currently evaluating the Rdlhomo5 models in regards to their performance for molecular docking in the NCA-II site. Our results show that several models based on different templates must be evaluated to obtain a trustworthy structure for the application of structure-based virtual screening in insect GABAA-R homology models.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Sociedad Argentina de Biofísica
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Molecular docking
dc.subject
Virtual screening
dc.subject
Homology modelling
dc.subject
Gabaergic insecticides
dc.subject.classification
Biofísica
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Assessment of insect GABAA receptor homology models performance for virtual screening and their validation by molecular dynamics simulations
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/conferenceObject
dc.type
info:ar-repo/semantics/documento de conferencia
dc.date.updated
2022-11-09T17:03:32Z
dc.journal.pagination
60-60
dc.journal.pais
Argentina
dc.journal.ciudad
Buenos Aires
dc.description.fil
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
dc.description.fil
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
dc.description.fil
Fil: Villarreal, Marcos Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
dc.description.fil
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
dc.description.fil
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
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
dc.conicet.rol
Autor
dc.conicet.rol
Autor
dc.conicet.rol
Autor
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Autor
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Autor
dc.conicet.nroedicion
1
dc.coverage
Nacional
dc.type.subtype
Virtual
dc.description.nombreEvento
Biofísica en tiempos de COVID-19 : Primeras Jornadas Virtuales SAB 2020
dc.date.evento
2020-12-03
dc.description.ciudadEvento
Buenos Aires
dc.description.paisEvento
Argentina
dc.type.publicacion
Book
dc.description.institucionOrganizadora
Sociedad Argentina de Biofísica
dc.source.libro
Sociedad Argentina de Biofísica. Biofísica en tiempos de COVID-19 : Primeras Jornadas Virtuales SAB 2020
dc.date.eventoHasta
2020-12-04
dc.type
Virtual
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