Challenges of docking in large, flexible and promiscuous binding sites

After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: i) the sizes of the binding site and the ligand; ii) the flexibility of both interacting partners, and iii) the differential sol...

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Detalles Bibliográficos
Autores: Kotev, Martin, Soliva, Robert, Orozco López, Modesto
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/110714
Acceso en línea:https://hdl.handle.net/2445/110714
Access Level:acceso abierto
Palabra clave:Associació molecular
Lligands (Bioquímica)
Fixació de proteïnes
Molecular association
Ligands (Biochemistry)
Protein binding
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spelling Challenges of docking in large, flexible and promiscuous binding sitesKotev, MartinSoliva, RobertOrozco López, ModestoAssociació molecularLligands (Bioquímica)Fixació de proteïnesMolecular associationLigands (Biochemistry)Protein bindingAfter decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: i) the sizes of the binding site and the ligand; ii) the flexibility of both interacting partners, and iii) the differential solvation of bound and unbound partners. We have evaluated the performance of standard rigid(receptor)/flexible(ligand) docking approaches with respect to last-generation fully flexible docking methods to obtain reasonable poses in a very challenging case: soluble Epoxide Hydrolase (sEH), a flexible protein showing different binding sites. We found that full description of the flexibility of both protein and ligand and accurate description of solvation leads to significant improvement in the ability of docking to reproduce well known binding modes, and at the same time capture the intrinsic binding promiscuity of the protein.Elsevier2017201820162017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion9 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/110714Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1016/j.bmc.2016.08.010Bioorganic & Medicinal Chemistry, 2016, vol. 24, num. 20, p. 4961-4969https://doi.org/10.1016/j.bmc.2016.08.010info:eu-repo/grantAgreement/EC/H2020/675728cc-by-nc-nd (c) Elsevier, 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1107142026-05-29T05:05:01Z
dc.title.none.fl_str_mv Challenges of docking in large, flexible and promiscuous binding sites
title Challenges of docking in large, flexible and promiscuous binding sites
spellingShingle Challenges of docking in large, flexible and promiscuous binding sites
Kotev, Martin
Associació molecular
Lligands (Bioquímica)
Fixació de proteïnes
Molecular association
Ligands (Biochemistry)
Protein binding
title_short Challenges of docking in large, flexible and promiscuous binding sites
title_full Challenges of docking in large, flexible and promiscuous binding sites
title_fullStr Challenges of docking in large, flexible and promiscuous binding sites
title_full_unstemmed Challenges of docking in large, flexible and promiscuous binding sites
title_sort Challenges of docking in large, flexible and promiscuous binding sites
dc.creator.none.fl_str_mv Kotev, Martin
Soliva, Robert
Orozco López, Modesto
author Kotev, Martin
author_facet Kotev, Martin
Soliva, Robert
Orozco López, Modesto
author_role author
author2 Soliva, Robert
Orozco López, Modesto
author2_role author
author
dc.subject.none.fl_str_mv Associació molecular
Lligands (Bioquímica)
Fixació de proteïnes
Molecular association
Ligands (Biochemistry)
Protein binding
topic Associació molecular
Lligands (Bioquímica)
Fixació de proteïnes
Molecular association
Ligands (Biochemistry)
Protein binding
description After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: i) the sizes of the binding site and the ligand; ii) the flexibility of both interacting partners, and iii) the differential solvation of bound and unbound partners. We have evaluated the performance of standard rigid(receptor)/flexible(ligand) docking approaches with respect to last-generation fully flexible docking methods to obtain reasonable poses in a very challenging case: soluble Epoxide Hydrolase (sEH), a flexible protein showing different binding sites. We found that full description of the flexibility of both protein and ligand and accurate description of solvation leads to significant improvement in the ability of docking to reproduce well known binding modes, and at the same time capture the intrinsic binding promiscuity of the protein.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/110714
url https://hdl.handle.net/2445/110714
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.bmc.2016.08.010
Bioorganic & Medicinal Chemistry, 2016, vol. 24, num. 20, p. 4961-4969
https://doi.org/10.1016/j.bmc.2016.08.010
info:eu-repo/grantAgreement/EC/H2020/675728
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier, 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier, 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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