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dc.contributor.authorPérez González, Juan Jesús
dc.contributor.authorLupala, Cecylia Severin
dc.contributor.authorGomez-Gutierrez, Patricia
dc.contributor.otherUniversitat Politècnica de Catalunya. Departament d'Enginyeria Química
dc.date.accessioned2017-02-01T08:46:54Z
dc.date.available2018-07-03T00:30:40Z
dc.date.issued2016-07-21
dc.identifier.citationPerez, J., S. Lupala, C., Gomez-Gutierrez, P. New insights into the stereochemical requirements of the bradykinin B1 receptor antagonist binding. "Journal of molecular graphics and modeling", 21 Juliol 2016, vol. 68, p. 184-196.
dc.identifier.issn1093-3263
dc.identifier.urihttp://hdl.handle.net/2117/100418
dc.description.abstractBradykinin (BK) is a nonapeptide involved in several pathophysiological conditions including among others, septic and haemorrhagic shock, anaphylaxis, arthritis, rhinitis, asthma, inflammatory bowel disease. Accordingly, BK antagonists have long been sought after for therapeutic intervention. Action of BK is mediated through two different G-protein coupled receptors known as B1 and B2. Although there are several B1 antagonists reported in literature, their pharmacological profile is not yet optimal so that new molecules need to be discovered. In the present work we have constructed an atomistic model of the B1 receptor and docked diverse available non-peptide antagonists in order to get a deeper insight into the structure-activity relationships involving binding to this receptor. The model was constructed by homology modelling using the chemokine CXC4 and bovine rhodopsin receptors as template. The model was further refined using molecular dynamics for 600 ns with the protein embedded in a POPC bilayer. From the refinement process we obtained an average structure that was used for docking studies using the Glide software. Antagonists selected for the docking studies include Compound 11, Compound 12, Chroman28, SSR240612, NPV-SAA164 and PS020990. The results of the docking study underline the role of specific receptor residues in ligand binding. The results of this study permitted to define a pharmacophore that describes the stereochemical requirements of antagonist binding, and can be used for the discovery of new compounds.
dc.format.extent13 p.
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.subjectÀrees temàtiques de la UPC::Enginyeria química
dc.subject.lcshBradykinin--Antagonists
dc.subject.lcshG proteins--Receptors
dc.subject.otherBradiquina
dc.subject.otherantagonistes
dc.subject.otherdisseny de farmacs per ordinador
dc.subject.otherreceptors acoblats a proteïnes G
dc.titleNew insights into the stereochemical requirements of the bradykinin B1 receptor antagonist binding
dc.typeArticle
dc.subject.lemacFarmacologia molecular
dc.subject.lemacProteïnes G -- Receptors
dc.contributor.groupUniversitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial
dc.identifier.doi10.1016/j.jmgm.2016.06.010
dc.description.peerreviewedPeer Reviewed
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S1093326316301048
dc.rights.accessOpen Access
local.identifier.drac19330208
dc.description.versionPostprint (author's final draft)
local.citation.authorPerez, J.; S. Lupala, C.; Gomez-Gutierrez, P.
local.citation.publicationNameJournal of molecular graphics and modeling
local.citation.volume68
local.citation.startingPage184
local.citation.endingPage196


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