Purposely engineered drug-target mismatches for entropy-based drug optimization

Autores
Fernandez, Ariel; Fraser, Christopher; Ridgway, Scott L.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Proteins are dynamic objects, often undergoing significant structural change and reducing their conformational possibilities upon binding to a ligand. Thus, unless dynamic information is incorporated, structure-based drug design becomes of limited applicability. Even within a dynamic approach, a rarely visited scenario arises as proteins increase their entropy content upon binding by locally enhancing conformational exploration in the complex. We argue that this binding mode is of primary importance in drug development, since it allows for drugs that are not optimized in the conventional way but feature mismatches with the target, suggesting a new class of molecular design based on entropy optimization. This possibility is illustrated in this opinion piece, which advocates the exploitation of dynamic information for drug design.
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; Argentina
Fil: Fraser, Christopher. University Of Chicago; Estados Unidos
Fil: Ridgway, Scott L.. University Of Chicago; Estados Unidos
Materia
Molecular Pharmacology
Rational Drug Design
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:11336/18928

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spelling Purposely engineered drug-target mismatches for entropy-based drug optimizationFernandez, ArielFraser, ChristopherRidgway, Scott L.Molecular PharmacologyRational Drug Designhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Proteins are dynamic objects, often undergoing significant structural change and reducing their conformational possibilities upon binding to a ligand. Thus, unless dynamic information is incorporated, structure-based drug design becomes of limited applicability. Even within a dynamic approach, a rarely visited scenario arises as proteins increase their entropy content upon binding by locally enhancing conformational exploration in the complex. We argue that this binding mode is of primary importance in drug development, since it allows for drugs that are not optimized in the conventional way but feature mismatches with the target, suggesting a new class of molecular design based on entropy optimization. This possibility is illustrated in this opinion piece, which advocates the exploitation of dynamic information for drug design.Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; ArgentinaFil: Fraser, Christopher. University Of Chicago; Estados UnidosFil: Ridgway, Scott L.. University Of Chicago; Estados UnidosElsevier Science London2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18928Fernandez, Ariel; Fraser, Christopher; Ridgway, Scott L.; Purposely engineered drug-target mismatches for entropy-based drug optimization; Elsevier Science London; Trends In Biotechnology; 30; 1; 1-2012; 1-70167-7799CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0167779911001338info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tibtech.2011.07.003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:46Zoai:ri.conicet.gov.ar:11336/18928instacron: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 09:39:46.575CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Purposely engineered drug-target mismatches for entropy-based drug optimization
title Purposely engineered drug-target mismatches for entropy-based drug optimization
spellingShingle Purposely engineered drug-target mismatches for entropy-based drug optimization
Fernandez, Ariel
Molecular Pharmacology
Rational Drug Design
title_short Purposely engineered drug-target mismatches for entropy-based drug optimization
title_full Purposely engineered drug-target mismatches for entropy-based drug optimization
title_fullStr Purposely engineered drug-target mismatches for entropy-based drug optimization
title_full_unstemmed Purposely engineered drug-target mismatches for entropy-based drug optimization
title_sort Purposely engineered drug-target mismatches for entropy-based drug optimization
dc.creator.none.fl_str_mv Fernandez, Ariel
Fraser, Christopher
Ridgway, Scott L.
author Fernandez, Ariel
author_facet Fernandez, Ariel
Fraser, Christopher
Ridgway, Scott L.
author_role author
author2 Fraser, Christopher
Ridgway, Scott L.
author2_role author
author
dc.subject.none.fl_str_mv Molecular Pharmacology
Rational Drug Design
topic Molecular Pharmacology
Rational Drug Design
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Proteins are dynamic objects, often undergoing significant structural change and reducing their conformational possibilities upon binding to a ligand. Thus, unless dynamic information is incorporated, structure-based drug design becomes of limited applicability. Even within a dynamic approach, a rarely visited scenario arises as proteins increase their entropy content upon binding by locally enhancing conformational exploration in the complex. We argue that this binding mode is of primary importance in drug development, since it allows for drugs that are not optimized in the conventional way but feature mismatches with the target, suggesting a new class of molecular design based on entropy optimization. This possibility is illustrated in this opinion piece, which advocates the exploitation of dynamic information for drug design.
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; Argentina
Fil: Fraser, Christopher. University Of Chicago; Estados Unidos
Fil: Ridgway, Scott L.. University Of Chicago; Estados Unidos
description Proteins are dynamic objects, often undergoing significant structural change and reducing their conformational possibilities upon binding to a ligand. Thus, unless dynamic information is incorporated, structure-based drug design becomes of limited applicability. Even within a dynamic approach, a rarely visited scenario arises as proteins increase their entropy content upon binding by locally enhancing conformational exploration in the complex. We argue that this binding mode is of primary importance in drug development, since it allows for drugs that are not optimized in the conventional way but feature mismatches with the target, suggesting a new class of molecular design based on entropy optimization. This possibility is illustrated in this opinion piece, which advocates the exploitation of dynamic information for drug design.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/18928
Fernandez, Ariel; Fraser, Christopher; Ridgway, Scott L.; Purposely engineered drug-target mismatches for entropy-based drug optimization; Elsevier Science London; Trends In Biotechnology; 30; 1; 1-2012; 1-7
0167-7799
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18928
identifier_str_mv Fernandez, Ariel; Fraser, Christopher; Ridgway, Scott L.; Purposely engineered drug-target mismatches for entropy-based drug optimization; Elsevier Science London; Trends In Biotechnology; 30; 1; 1-2012; 1-7
0167-7799
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://www.sciencedirect.com/science/article/pii/S0167779911001338
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tibtech.2011.07.003
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
dc.publisher.none.fl_str_mv Elsevier Science London
publisher.none.fl_str_mv Elsevier Science London
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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