Aromatic clusters in protein-protein and protein-drug complexes

Autores
Lanzarotti, Esteban Omar; Defelipe, Lucas Alfredo; Marti, Marcelo Adrian; Turjanski, Adrian
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein-drug and protein-protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein-protein and protein-drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein-drug and protein-protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein-protein and protein-drug complexes, and suggest that protein-protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein-drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein-drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.
Fil: Lanzarotti, Esteban Omar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Defelipe, Lucas Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Turjanski, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
AROMATIC INTERACTIONS
PROTEIN-DRUG INTERACTIONS
PROTEIN-PROTEIN INTERACTIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/143936
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/143936
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Aromatic clusters in protein-protein and protein-drug complexesLanzarotti, Esteban OmarDefelipe, Lucas AlfredoMarti, Marcelo AdrianTurjanski, AdrianAROMATIC INTERACTIONSPROTEIN-DRUG INTERACTIONSPROTEIN-PROTEIN INTERACTIONShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein-drug and protein-protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein-protein and protein-drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein-drug and protein-protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein-protein and protein-drug complexes, and suggest that protein-protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein-drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein-drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.Fil: Lanzarotti, Esteban Omar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Defelipe, Lucas Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Turjanski, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaBioMed Central2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/143936Lanzarotti, Esteban Omar; Defelipe, Lucas Alfredo; Marti, Marcelo Adrian; Turjanski, Adrian; Aromatic clusters in protein-protein and protein-drug complexes; BioMed Central; Journal of Cheminformatics; 12; 1; 5-2020; 1-91758-2946CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jcheminf.biomedcentral.com/articles/10.1186/s13321-020-00437-4info:eu-repo/semantics/altIdentifier/doi/10.1186/s13321-020-00437-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:38Zoai:ri.conicet.gov.ar:11336/143936instacron: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:34982025-09-29 10:01:38.608CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aromatic clusters in protein-protein and protein-drug complexes
title Aromatic clusters in protein-protein and protein-drug complexes
spellingShingle Aromatic clusters in protein-protein and protein-drug complexes
Lanzarotti, Esteban Omar
AROMATIC INTERACTIONS
PROTEIN-DRUG INTERACTIONS
PROTEIN-PROTEIN INTERACTIONS
title_short Aromatic clusters in protein-protein and protein-drug complexes
title_full Aromatic clusters in protein-protein and protein-drug complexes
title_fullStr Aromatic clusters in protein-protein and protein-drug complexes
title_full_unstemmed Aromatic clusters in protein-protein and protein-drug complexes
title_sort Aromatic clusters in protein-protein and protein-drug complexes
dc.creator.none.fl_str_mv Lanzarotti, Esteban Omar
Defelipe, Lucas Alfredo
Marti, Marcelo Adrian
Turjanski, Adrian
author Lanzarotti, Esteban Omar
author_facet Lanzarotti, Esteban Omar
Defelipe, Lucas Alfredo
Marti, Marcelo Adrian
Turjanski, Adrian
author_role author
author2 Defelipe, Lucas Alfredo
Marti, Marcelo Adrian
Turjanski, Adrian
author2_role author
author
author
dc.subject.none.fl_str_mv AROMATIC INTERACTIONS
PROTEIN-DRUG INTERACTIONS
PROTEIN-PROTEIN INTERACTIONS
topic AROMATIC INTERACTIONS
PROTEIN-DRUG INTERACTIONS
PROTEIN-PROTEIN INTERACTIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein-drug and protein-protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein-protein and protein-drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein-drug and protein-protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein-protein and protein-drug complexes, and suggest that protein-protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein-drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein-drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.
Fil: Lanzarotti, Esteban Omar. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Defelipe, Lucas Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Turjanski, Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein-drug and protein-protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein-protein and protein-drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein-drug and protein-protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein-protein and protein-drug complexes, and suggest that protein-protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein-drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein-drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
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/11336/143936
Lanzarotti, Esteban Omar; Defelipe, Lucas Alfredo; Marti, Marcelo Adrian; Turjanski, Adrian; Aromatic clusters in protein-protein and protein-drug complexes; BioMed Central; Journal of Cheminformatics; 12; 1; 5-2020; 1-9
1758-2946
CONICET Digital
CONICET
url http://hdl.handle.net/11336/143936
identifier_str_mv Lanzarotti, Esteban Omar; Defelipe, Lucas Alfredo; Marti, Marcelo Adrian; Turjanski, Adrian; Aromatic clusters in protein-protein and protein-drug complexes; BioMed Central; Journal of Cheminformatics; 12; 1; 5-2020; 1-9
1758-2946
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://jcheminf.biomedcentral.com/articles/10.1186/s13321-020-00437-4
info:eu-repo/semantics/altIdentifier/doi/10.1186/s13321-020-00437-4
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
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
_version_ 1844613811895533568
score 13.070432

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