Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description

Autores
Spyrakis, Francesca; Cavasotto, Claudio Norberto
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical “structural” issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns.
Fil: Spyrakis, Francesca. Università degli Studi di Modena e Reggio Emilia; Italia
Fil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Materia
Homology Modeling
Virtual Screening
Docking
Structure-Based Drug Design
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12309
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules descriptionSpyrakis, FrancescaCavasotto, Claudio NorbertoHomology ModelingVirtual ScreeningDockingStructure-Based Drug Designhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical “structural” issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns.Fil: Spyrakis, Francesca. Università degli Studi di Modena e Reggio Emilia; ItaliaFil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaElsevier2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdftext/plainapplication/pdfhttp://hdl.handle.net/11336/12309Spyrakis, Francesca; Cavasotto, Claudio Norberto; Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description; Elsevier; Archives Of Biochemistry And Biophysics; 583; 10-2015; 105-1190003-9861enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S000398611530028Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2015.08.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:09:51Zoai:ri.conicet.gov.ar:11336/12309instacron: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 10:09:51.711CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
title Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
spellingShingle Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
Spyrakis, Francesca
Homology Modeling
Virtual Screening
Docking
Structure-Based Drug Design
title_short Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
title_full Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
title_fullStr Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
title_full_unstemmed Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
title_sort Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
dc.creator.none.fl_str_mv Spyrakis, Francesca
Cavasotto, Claudio Norberto
author Spyrakis, Francesca
author_facet Spyrakis, Francesca
Cavasotto, Claudio Norberto
author_role author
author2 Cavasotto, Claudio Norberto
author2_role author
dc.subject.none.fl_str_mv Homology Modeling
Virtual Screening
Docking
Structure-Based Drug Design
topic Homology Modeling
Virtual Screening
Docking
Structure-Based Drug Design
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical “structural” issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns.
Fil: Spyrakis, Francesca. Università degli Studi di Modena e Reggio Emilia; Italia
Fil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
description Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical “structural” issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
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/11336/12309
Spyrakis, Francesca; Cavasotto, Claudio Norberto; Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description; Elsevier; Archives Of Biochemistry And Biophysics; 583; 10-2015; 105-119
0003-9861
url http://hdl.handle.net/11336/12309
identifier_str_mv Spyrakis, Francesca; Cavasotto, Claudio Norberto; Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description; Elsevier; Archives Of Biochemistry And Biophysics; 583; 10-2015; 105-119
0003-9861
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/S000398611530028X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.abb.2015.08.002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
text/plain
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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score 13.070432

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