Mostra el registre d'ítem simple

dc.contributor.authorGómez Gutierrez, Patricia
dc.contributor.authorRubio Martínez, Jaime
dc.contributor.authorPérez González, Juan Jesús
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Enginyeria Química
dc.date.accessioned2017-12-20T11:38:01Z
dc.date.available2017-12-20T11:38:01Z
dc.date.issued2017-10-23
dc.identifier.citationGomez-Gutierrez, P., Rubio, J., Perez, J. Identification of potential small molecule binding pockets in p38a MAP kinase. "Journal of chemical information and modeling", 23 Octubre 2017, vol. 57, núm. 10, p. 2566-2574.
dc.identifier.issn1549-9596
dc.identifier.urihttp://hdl.handle.net/2117/112322
dc.description.abstractGiven the essential role played by protein kinases in regulating cellular pathways, their dysregulation can result in the onset and/or progression of various human diseases. Structural analysis of diverse protein kinases suggests that these proteins exhibit a remarkable plasticity that allows them to adopt distinct conformations in response to interactions with other proteins, providing an opportunity for designing allosteric modulators. The present work reports the results of an in silico screening study aimed at identifying novel prospective allosteric binding sites in the paradigmatic p38a MAP kinase. The process was carried out using a protein ensemble generated from a 6 µs accelerated molecular dynamics simulation. The results of this calculation were first used to study the flexibility of the protein using Principal Component Analysis, followed by a Cluster Analysis aimed at producing an ensemble of conformations representative of the sampling process. Representative structures of the diverse clusters were subsequently screened for hot spots using FTMAP. The procedure permitted the identification of diverse allosteric sites of p38a already described in the literature including the DFG pocket, the lipid binding pocket, the DEF site, the docking groove, the CD and ED sites, and the backside site as well as a novel site recently reported: the A-loop regulatory site. Furthermore, the study also permitted the identification of ten novel prospective allosteric sites named NP1 to NP10, involving in most of the cases protein structural elements that control kinase activation including the activation loop, the catalytic loop, the aC helix, the L16 loop, and the glycine-rich loop.
dc.format.extent9 p.
dc.language.isoeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Spain
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria química
dc.subject.lcshProteins
dc.titleIdentification of potential small molecule binding pockets in p38a MAP kinase
dc.typeArticle
dc.subject.lemacProteïnes
dc.contributor.groupUniversitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial
dc.identifier.doi10.1021/acs.jcim.7b00439
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://pubs.acs.org/doi/abs/10.1021/acs.jcim.7b00439
dc.rights.accessOpen Access
local.identifier.drac21589870
dc.description.versionPostprint (author's final draft)
local.citation.authorGomez-Gutierrez, P.; Rubio, J.; Perez, J.
local.citation.publicationNameJournal of chemical information and modeling
local.citation.volume57
local.citation.number10
local.citation.startingPage2566
local.citation.endingPage2574


Fitxers d'aquest items

Thumbnail

Aquest ítem apareix a les col·leccions següents

Mostra el registre d'ítem simple