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dc.contributor.authorKINSELLA, GEMMA
dc.contributor.authorROZAS, ISABEL
dc.contributor.authorWATSON, GRAEME WILLIAM
dc.date.accessioned2007-12-17T21:49:34Z
dc.date.available2007-12-17T21:49:34Z
dc.date.issued2005
dc.date.submitted2005en
dc.identifier.citationG. Kinsella, I. Rozas, G. Watson, Modelling the interaction of catecholamines with the alpha1A Adrenoceptor- towards a ligand-induced receptor structure, Journal of Computer-Aided Molecular Design, 19, (6), 2005, p357 - 367en
dc.identifier.otherYen
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/12841
dc.descriptionPUBLISHEDen
dc.description.abstractAdrenoceptors are members of the important G protein coupled receptor family for which the detailed mechanism of activation remains unclear. In this study, we have combined docking and molecular dynamics simulations to model the ligand induced effect on an homology derived human alpha1A adrenoceptor. Analysis of agonist/alpha1A adrenoceptor complex interactions focused on the role of the charged amine group, the aromatic ring, the N-methyl group of adrenaline, the beta hydroxyl group and the catechol meta and para hydroxyl groups of the catecholamines. The most critical interactions for the binding of the agonists are consistent with many earlier reports and our study suggests new residues possibly involved in the agonist-binding site, namely Thr-174 and Cys-176. We further observe a number of structural changes that occur upon agonist binding including a movement of TM-V away from TM-III and a change in the interactions of Asp-123 of the conserved DRY motif. This may cause Arg-124 to move out of the TM helical bundle and change the orientation of residues in IC-II and IC-III, allowing for increased affinity of coupling to the G-protein.en
dc.format.extent1108539 bytes
dc.format.extent357en
dc.format.extent367en
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.relation.ispartofseriesJournal of Computer-Aided Molecular Designen
dc.relation.ispartofseries19 (6), 2005en
dc.rightsYen
dc.subjectalpha1A-adrenoceptoren
dc.subjectagonistsen
dc.subjectmolecular dockingen
dc.subjectmolecular dynamicsen
dc.subjectreceptor activationen
dc.titleModelling the interaction of catecholamines with the alpha1A Adrenoceptor- towards a ligand-induced receptor structureen
dc.typeJournal Articleen
dc.contributor.sponsorHigher Education Authority
dc.contributor.sponsorEnterprise Irelanden
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/rozasi
dc.identifier.rssinternalid22677
dc.identifier.rssurihttp://www.springerlink.com/content/y265w4h706366l7x/fulltext.pdf
dc.identifier.rssurihttp://www.springerlink.com/content/y265w4h706366l7x/


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