Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis

Autores
Vettorazzi, Marcela Cristina; Menéndez, Cintia Anabella; Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Appignanesi, Gustavo Adrian; Enriz, Ricardo Daniel
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We report here the results of two theoretical models to predict the inhibitory effect of inhibitors of sphingosine kinase 1 that stand on different computational basis. The active site of SphK1 is a complex system and the ligands under the study possess a significant conformational flexibility; therefore for our study we performed extended simulations and proper clusterization process. The two theoretical approaches used here, hydrogen bond dynamics propensity analysis and Quantum Theory of Atoms in Molecules (QTAIM) calculations, exhibit excellent correlations with the experimental data. In the case of the hydrogen bond dynamics propensity analysis, it is remarkable that a rather simple methodology with low computational requirements yields results in excellent accord with experimental data. In turn QTAIM calculations are much more computational demanding and are also more complex and tedious for data analysis than the hydrogen bond dynamic propensity analysis. However, this greater computational effort is justified because the QTAIM study, in addition to giving an excellent correlation with the experimental data, also gives us valuable information about which parts or functional groups of the different ligands are those that should be replaced in order to improve the interactions and thereby to increase the affinity for SphK1. Our results indicate that both approaches can be very useful in order to predict the inhibiting effect of new compounds before they are synthesized.
Fil: Vettorazzi, Marcela Cristina. 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: Menéndez, Cintia Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: Gutierrez, Lucas Joel. 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: 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: Appignanesi, Gustavo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
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
HYDROGEN BOND DYNAMIC PROPENSITY ANALYSIS
QTAIM CALCULATIONS
SPHINGOSINE KINASE INHIBITORS
THEORETICAL APPROACHES
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:11336/86363
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysisVettorazzi, Marcela CristinaMenéndez, Cintia AnabellaGutierrez, Lucas JoelAndujar, Sebastian AntonioAppignanesi, Gustavo AdrianEnriz, Ricardo DanielHYDROGEN BOND DYNAMIC PROPENSITY ANALYSISQTAIM CALCULATIONSSPHINGOSINE KINASE INHIBITORSTHEORETICAL APPROACHEShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We report here the results of two theoretical models to predict the inhibitory effect of inhibitors of sphingosine kinase 1 that stand on different computational basis. The active site of SphK1 is a complex system and the ligands under the study possess a significant conformational flexibility; therefore for our study we performed extended simulations and proper clusterization process. The two theoretical approaches used here, hydrogen bond dynamics propensity analysis and Quantum Theory of Atoms in Molecules (QTAIM) calculations, exhibit excellent correlations with the experimental data. In the case of the hydrogen bond dynamics propensity analysis, it is remarkable that a rather simple methodology with low computational requirements yields results in excellent accord with experimental data. In turn QTAIM calculations are much more computational demanding and are also more complex and tedious for data analysis than the hydrogen bond dynamic propensity analysis. However, this greater computational effort is justified because the QTAIM study, in addition to giving an excellent correlation with the experimental data, also gives us valuable information about which parts or functional groups of the different ligands are those that should be replaced in order to improve the interactions and thereby to increase the affinity for SphK1. Our results indicate that both approaches can be very useful in order to predict the inhibiting effect of new compounds before they are synthesized.Fil: Vettorazzi, Marcela Cristina. 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: Menéndez, Cintia Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Gutierrez, Lucas Joel. 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: 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: Appignanesi, Gustavo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: 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; ArgentinaSpringer2018-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86363Vettorazzi, Marcela Cristina; Menéndez, Cintia Anabella; Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Appignanesi, Gustavo Adrian; et al.; Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis; Springer; Journal of Computer-Aided Molecular Design; 32; 7; 7-2018; 781-7910920-654XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s10822-018-0129-7info:eu-repo/semantics/altIdentifier/doi/10.1007/s10822-018-0129-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:38:25Zoai:ri.conicet.gov.ar:11336/86363instacron: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:34982025-10-29 11:38:25.694CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
title Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
spellingShingle Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
Vettorazzi, Marcela Cristina
HYDROGEN BOND DYNAMIC PROPENSITY ANALYSIS
QTAIM CALCULATIONS
SPHINGOSINE KINASE INHIBITORS
THEORETICAL APPROACHES
title_short Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
title_full Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
title_fullStr Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
title_full_unstemmed Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
title_sort Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis
dc.creator.none.fl_str_mv Vettorazzi, Marcela Cristina
Menéndez, Cintia Anabella
Gutierrez, Lucas Joel
Andujar, Sebastian Antonio
Appignanesi, Gustavo Adrian
Enriz, Ricardo Daniel
author Vettorazzi, Marcela Cristina
author_facet Vettorazzi, Marcela Cristina
Menéndez, Cintia Anabella
Gutierrez, Lucas Joel
Andujar, Sebastian Antonio
Appignanesi, Gustavo Adrian
Enriz, Ricardo Daniel
author_role author
author2 Menéndez, Cintia Anabella
Gutierrez, Lucas Joel
Andujar, Sebastian Antonio
Appignanesi, Gustavo Adrian
Enriz, Ricardo Daniel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv HYDROGEN BOND DYNAMIC PROPENSITY ANALYSIS
QTAIM CALCULATIONS
SPHINGOSINE KINASE INHIBITORS
THEORETICAL APPROACHES
topic HYDROGEN BOND DYNAMIC PROPENSITY ANALYSIS
QTAIM CALCULATIONS
SPHINGOSINE KINASE INHIBITORS
THEORETICAL APPROACHES
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 the results of two theoretical models to predict the inhibitory effect of inhibitors of sphingosine kinase 1 that stand on different computational basis. The active site of SphK1 is a complex system and the ligands under the study possess a significant conformational flexibility; therefore for our study we performed extended simulations and proper clusterization process. The two theoretical approaches used here, hydrogen bond dynamics propensity analysis and Quantum Theory of Atoms in Molecules (QTAIM) calculations, exhibit excellent correlations with the experimental data. In the case of the hydrogen bond dynamics propensity analysis, it is remarkable that a rather simple methodology with low computational requirements yields results in excellent accord with experimental data. In turn QTAIM calculations are much more computational demanding and are also more complex and tedious for data analysis than the hydrogen bond dynamic propensity analysis. However, this greater computational effort is justified because the QTAIM study, in addition to giving an excellent correlation with the experimental data, also gives us valuable information about which parts or functional groups of the different ligands are those that should be replaced in order to improve the interactions and thereby to increase the affinity for SphK1. Our results indicate that both approaches can be very useful in order to predict the inhibiting effect of new compounds before they are synthesized.
Fil: Vettorazzi, Marcela Cristina. 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: Menéndez, Cintia Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
Fil: Gutierrez, Lucas Joel. 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: 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: Appignanesi, Gustavo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
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 the results of two theoretical models to predict the inhibitory effect of inhibitors of sphingosine kinase 1 that stand on different computational basis. The active site of SphK1 is a complex system and the ligands under the study possess a significant conformational flexibility; therefore for our study we performed extended simulations and proper clusterization process. The two theoretical approaches used here, hydrogen bond dynamics propensity analysis and Quantum Theory of Atoms in Molecules (QTAIM) calculations, exhibit excellent correlations with the experimental data. In the case of the hydrogen bond dynamics propensity analysis, it is remarkable that a rather simple methodology with low computational requirements yields results in excellent accord with experimental data. In turn QTAIM calculations are much more computational demanding and are also more complex and tedious for data analysis than the hydrogen bond dynamic propensity analysis. However, this greater computational effort is justified because the QTAIM study, in addition to giving an excellent correlation with the experimental data, also gives us valuable information about which parts or functional groups of the different ligands are those that should be replaced in order to improve the interactions and thereby to increase the affinity for SphK1. Our results indicate that both approaches can be very useful in order to predict the inhibiting effect of new compounds before they are synthesized.
publishDate 2018
dc.date.none.fl_str_mv 2018-07
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/11336/86363
Vettorazzi, Marcela Cristina; Menéndez, Cintia Anabella; Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Appignanesi, Gustavo Adrian; et al.; Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis; Springer; Journal of Computer-Aided Molecular Design; 32; 7; 7-2018; 781-791
0920-654X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86363
identifier_str_mv Vettorazzi, Marcela Cristina; Menéndez, Cintia Anabella; Gutierrez, Lucas Joel; Andujar, Sebastian Antonio; Appignanesi, Gustavo Adrian; et al.; Theoretical models to predict the inhibitory effect of ligands of sphingosine kinase 1 using QTAIM calculations and hydrogen bond dynamic propensity analysis; Springer; Journal of Computer-Aided Molecular Design; 32; 7; 7-2018; 781-791
0920-654X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s10822-018-0129-7
info:eu-repo/semantics/altIdentifier/doi/10.1007/s10822-018-0129-7
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
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dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
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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