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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/18928
Ver los metadatos del registro completo
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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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1844613259036983296 |
score |
13.070432 |