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...

ver descrição completa

Detalhes bibliográficos
Autores: Kotev, Martin, Soliva, Robert, Orozco, Modesto
Formato: artículo
Fecha de publicación:2016
País:España
Recursos:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/90906
Acesso em linha:https://hdl.handle.net/2117/90906
https://dx.doi.org/10.1016/j.bmc.2016.08.010
Access Level:acceso abierto
Palavra-chave:Protein binding
Simulations
Induced-fit docking
PELE simulations
Soluble Epoxide Hydrolase
Benchmark
Proteïnes--Investigació
Simulació, Mètodes de
Àrees temàtiques de la UPC::Enginyeria biomèdica
id ES_4d36e8fb22a48fb77c2129fc14ce90f8
oai_identifier_str oai:upcommons.upc.edu:2117/90906
network_acronym_str ES
network_name_str España
repository_id_str
spelling Challenges of docking in large, flexible and promiscuous binding sitesKotev, MartinSoliva, RobertOrozco, ModestoProtein bindingSimulationsInduced-fit dockingPELE simulationsSoluble Epoxide HydrolaseBenchmarkProteïnes--InvestigacióSimulació, Mètodes deÀrees temàtiques de la UPC::Enginyeria biomèdicaAfter 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.Peer ReviewedElsevier20162016-10-1520162016-10-20journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/90906https://dx.doi.org/10.1016/j.bmc.2016.08.010reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)InglésengMinisterio de Economía y Competitividad http://doi.org/10.13039/501100003329 BIO2015-64802-R ESTUDIO DE FORMAS INUSUALES Y TENSIONADAS DE LOS ACIDOS NUCLEICOS DE INTERES BIOMEDICO Y BIOTECNOLOGICO.European Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 675728 Centre of Excellence for Biomolecular Researchopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/909062026-05-27T15:37:01Z
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
Protein binding
Simulations
Induced-fit docking
PELE simulations
Soluble Epoxide Hydrolase
Benchmark
Proteïnes--Investigació
Simulació, Mètodes de
Àrees temàtiques de la UPC::Enginyeria biomèdica
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, Modesto
author Kotev, Martin
author_facet Kotev, Martin
Soliva, Robert
Orozco, Modesto
author_role author
author2 Soliva, Robert
Orozco, Modesto
author2_role author
author
dc.subject.none.fl_str_mv Protein binding
Simulations
Induced-fit docking
PELE simulations
Soluble Epoxide Hydrolase
Benchmark
Proteïnes--Investigació
Simulació, Mètodes de
Àrees temàtiques de la UPC::Enginyeria biomèdica
topic Protein binding
Simulations
Induced-fit docking
PELE simulations
Soluble Epoxide Hydrolase
Benchmark
Proteïnes--Investigació
Simulació, Mètodes de
Àrees temàtiques de la UPC::Enginyeria biomèdica
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
2016-10-15
2016
2016-10-20
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/90906
https://dx.doi.org/10.1016/j.bmc.2016.08.010
url https://hdl.handle.net/2117/90906
https://dx.doi.org/10.1016/j.bmc.2016.08.010
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://doi.org/10.13039/501100003329 BIO2015-64802-R ESTUDIO DE FORMAS INUSUALES Y TENSIONADAS DE LOS ACIDOS NUCLEICOS DE INTERES BIOMEDICO Y BIOTECNOLOGICO.
European Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 675728 Centre of Excellence for Biomolecular Research
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407677425123328
score 15.300719

Registos relacionados