Targeting Protein Pockets with Halogen Bonds

Autores
Bogado, María Lucrecia; Villafañe, Roxana Noelia; Angelina, Emilio Luis; Peruchena, Nelida Maria
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Halogen bonds (X-bonds) are directional interactions involving an attractive force between an electrophilic region on the halogen and interaction partners with nucleophilic properties, X-bond has gained recognition as an atypical molecular interaction useful in modeling halogens computationally to develop new pharmaceutical drugs. X-bonds in protein-ligand complexes are surrounded by residues that conforms the “X-bond environment”. Since sigma-hole formation in X-bonds is a consequence of the anisotropy of the charge density distribution around the halogen, protein residues that surround halogen atom might perturb its charge distribution and X-bond strength. In this work we proposed a protocol to study the feasibility of protein pockets to form X-bond with halogenated ligands, based on the environment. First, a structural survey of X-bonded protein-ligand complexes in public databases was performed to get a description of the “X- bond environment” based on the charge density, with help of the Quantum Theory of Atoms in Molecules (QTAIM). In the second step, the “X-bond environment” is used as a reference system to judge the propensity of protein pockets to host an X-bond. To test the protocol, we generated poses in which chlorobenzene is forming: (a) the known X-bond and (b) a different X-bond in a nearby protein sub-pocket with no structural evidence about its existence. We termed this last as “decoy X-bond”. Fifty poses were generated with the docking algorithm for both known and decoys X-bonds. Charge density-based X-bond environments for the docking poses were estimated by mapping the chloro protein neighborhood, into the X-bond environment pre-computed on the reference system. The protocol was able to prioritize docking poses that reproduce the actual X-bond in crystal structures based on their X-bond environments, since "real X-bonds" have stronger X-bond environments that decoy X-bonds, as expected. The results suggest that X-bond formation might require a proper protein environment to be established.
Fil: Bogado, María Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Villafañe, Roxana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
2nd Women in Bioinformatics & Data Science LA Conference
Buenos Aires
Argentina
Women in Bioinformatics & Data Science
Materia
HALOGEN-BOND
DRUG-DESIGN
X-BOND
QTAIM
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:11336/171977
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Targeting Protein Pockets with Halogen BondsBogado, María LucreciaVillafañe, Roxana NoeliaAngelina, Emilio LuisPeruchena, Nelida MariaHALOGEN-BONDDRUG-DESIGNX-BONDQTAIMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Halogen bonds (X-bonds) are directional interactions involving an attractive force between an electrophilic region on the halogen and interaction partners with nucleophilic properties, X-bond has gained recognition as an atypical molecular interaction useful in modeling halogens computationally to develop new pharmaceutical drugs. X-bonds in protein-ligand complexes are surrounded by residues that conforms the “X-bond environment”. Since sigma-hole formation in X-bonds is a consequence of the anisotropy of the charge density distribution around the halogen, protein residues that surround halogen atom might perturb its charge distribution and X-bond strength. In this work we proposed a protocol to study the feasibility of protein pockets to form X-bond with halogenated ligands, based on the environment. First, a structural survey of X-bonded protein-ligand complexes in public databases was performed to get a description of the “X- bond environment” based on the charge density, with help of the Quantum Theory of Atoms in Molecules (QTAIM). In the second step, the “X-bond environment” is used as a reference system to judge the propensity of protein pockets to host an X-bond. To test the protocol, we generated poses in which chlorobenzene is forming: (a) the known X-bond and (b) a different X-bond in a nearby protein sub-pocket with no structural evidence about its existence. We termed this last as “decoy X-bond”. Fifty poses were generated with the docking algorithm for both known and decoys X-bonds. Charge density-based X-bond environments for the docking poses were estimated by mapping the chloro protein neighborhood, into the X-bond environment pre-computed on the reference system. The protocol was able to prioritize docking poses that reproduce the actual X-bond in crystal structures based on their X-bond environments, since "real X-bonds" have stronger X-bond environments that decoy X-bonds, as expected. The results suggest that X-bond formation might require a proper protein environment to be established.Fil: Bogado, María Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Villafañe, Roxana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina2nd Women in Bioinformatics & Data Science LA ConferenceBuenos AiresArgentinaWomen in Bioinformatics & Data ScienceWomen in Bioinformatics & Data Science2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciatext/plainapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/171977Targeting Protein Pockets with Halogen Bonds; 2nd Women in Bioinformatics & Data Science LA Conference; Buenos Aires; Argentina; 2021; 119-119CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://wbds.la/conferences/2WBDSLAC/index.htmlInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:18Zoai:ri.conicet.gov.ar:11336/171977instacron: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:34982025-09-03 10:01:18.324CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Targeting Protein Pockets with Halogen Bonds
title Targeting Protein Pockets with Halogen Bonds
spellingShingle Targeting Protein Pockets with Halogen Bonds
Bogado, María Lucrecia
HALOGEN-BOND
DRUG-DESIGN
X-BOND
QTAIM
title_short Targeting Protein Pockets with Halogen Bonds
title_full Targeting Protein Pockets with Halogen Bonds
title_fullStr Targeting Protein Pockets with Halogen Bonds
title_full_unstemmed Targeting Protein Pockets with Halogen Bonds
title_sort Targeting Protein Pockets with Halogen Bonds
dc.creator.none.fl_str_mv Bogado, María Lucrecia
Villafañe, Roxana Noelia
Angelina, Emilio Luis
Peruchena, Nelida Maria
author Bogado, María Lucrecia
author_facet Bogado, María Lucrecia
Villafañe, Roxana Noelia
Angelina, Emilio Luis
Peruchena, Nelida Maria
author_role author
author2 Villafañe, Roxana Noelia
Angelina, Emilio Luis
Peruchena, Nelida Maria
author2_role author
author
author
dc.subject.none.fl_str_mv HALOGEN-BOND
DRUG-DESIGN
X-BOND
QTAIM
topic HALOGEN-BOND
DRUG-DESIGN
X-BOND
QTAIM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Halogen bonds (X-bonds) are directional interactions involving an attractive force between an electrophilic region on the halogen and interaction partners with nucleophilic properties, X-bond has gained recognition as an atypical molecular interaction useful in modeling halogens computationally to develop new pharmaceutical drugs. X-bonds in protein-ligand complexes are surrounded by residues that conforms the “X-bond environment”. Since sigma-hole formation in X-bonds is a consequence of the anisotropy of the charge density distribution around the halogen, protein residues that surround halogen atom might perturb its charge distribution and X-bond strength. In this work we proposed a protocol to study the feasibility of protein pockets to form X-bond with halogenated ligands, based on the environment. First, a structural survey of X-bonded protein-ligand complexes in public databases was performed to get a description of the “X- bond environment” based on the charge density, with help of the Quantum Theory of Atoms in Molecules (QTAIM). In the second step, the “X-bond environment” is used as a reference system to judge the propensity of protein pockets to host an X-bond. To test the protocol, we generated poses in which chlorobenzene is forming: (a) the known X-bond and (b) a different X-bond in a nearby protein sub-pocket with no structural evidence about its existence. We termed this last as “decoy X-bond”. Fifty poses were generated with the docking algorithm for both known and decoys X-bonds. Charge density-based X-bond environments for the docking poses were estimated by mapping the chloro protein neighborhood, into the X-bond environment pre-computed on the reference system. The protocol was able to prioritize docking poses that reproduce the actual X-bond in crystal structures based on their X-bond environments, since "real X-bonds" have stronger X-bond environments that decoy X-bonds, as expected. The results suggest that X-bond formation might require a proper protein environment to be established.
Fil: Bogado, María Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Villafañe, Roxana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Peruchena, Nelida Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
2nd Women in Bioinformatics & Data Science LA Conference
Buenos Aires
Argentina
Women in Bioinformatics & Data Science
description Halogen bonds (X-bonds) are directional interactions involving an attractive force between an electrophilic region on the halogen and interaction partners with nucleophilic properties, X-bond has gained recognition as an atypical molecular interaction useful in modeling halogens computationally to develop new pharmaceutical drugs. X-bonds in protein-ligand complexes are surrounded by residues that conforms the “X-bond environment”. Since sigma-hole formation in X-bonds is a consequence of the anisotropy of the charge density distribution around the halogen, protein residues that surround halogen atom might perturb its charge distribution and X-bond strength. In this work we proposed a protocol to study the feasibility of protein pockets to form X-bond with halogenated ligands, based on the environment. First, a structural survey of X-bonded protein-ligand complexes in public databases was performed to get a description of the “X- bond environment” based on the charge density, with help of the Quantum Theory of Atoms in Molecules (QTAIM). In the second step, the “X-bond environment” is used as a reference system to judge the propensity of protein pockets to host an X-bond. To test the protocol, we generated poses in which chlorobenzene is forming: (a) the known X-bond and (b) a different X-bond in a nearby protein sub-pocket with no structural evidence about its existence. We termed this last as “decoy X-bond”. Fifty poses were generated with the docking algorithm for both known and decoys X-bonds. Charge density-based X-bond environments for the docking poses were estimated by mapping the chloro protein neighborhood, into the X-bond environment pre-computed on the reference system. The protocol was able to prioritize docking poses that reproduce the actual X-bond in crystal structures based on their X-bond environments, since "real X-bonds" have stronger X-bond environments that decoy X-bonds, as expected. The results suggest that X-bond formation might require a proper protein environment to be established.
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
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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/11336/171977
Targeting Protein Pockets with Halogen Bonds; 2nd Women in Bioinformatics & Data Science LA Conference; Buenos Aires; Argentina; 2021; 119-119
CONICET Digital
CONICET
url http://hdl.handle.net/11336/171977
identifier_str_mv Targeting Protein Pockets with Halogen Bonds; 2nd Women in Bioinformatics & Data Science LA Conference; Buenos Aires; Argentina; 2021; 119-119
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://wbds.la/conferences/2WBDSLAC/index.html
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dc.format.none.fl_str_mv text/plain
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Women in Bioinformatics & Data Science
publisher.none.fl_str_mv Women in Bioinformatics & Data Science
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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