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dc.contributor.authorDilcan, Gonca
dc.contributor.authorDoruker, Pemra
dc.contributor.authorAkten, Ebru Demet
dc.date.accessioned2019-06-27T08:01:13Z
dc.date.available2019-06-27T08:01:13Z
dc.date.issued2019
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.urihttps://hdl.handle.net/20.500.12469/304
dc.identifier.urihttps://doi.org/10.1111/cbdd.13478
dc.description.abstractThis study investigates the structural distinctiveness of orthosteric ligand-binding sites of several human beta(2) adrenergic receptor (beta(2)-AR) conformations that have been obtained from a set of independent molecular dynamics (MD) simulations in the presence of intracellular loop 3 (ICL3). A docking protocol was established in order to classify each receptor conformation via its binding affinity to selected ligands with known efficacy. This work's main goal was to reveal many subtle features of the ligand-binding site presenting alternative conformations which might be considered as either active- or inactive-like but mostly specific for that ligand. Agonists inverse agonists and antagonists were docked to each MD conformer with distinct binding pockets using different docking tools and scoring functions. Mostly favored receptor conformation persistently observed in all docking/scoring evaluations was classified as active or inactive based on the type of ligand's biological effect. Classified MD conformers were further tested for their ability to discriminate agonists from inverse agonists/antagonists and several conformers were proposed as important targets to be used in virtual screening experiments that were often limited to a single X-ray structure.
dc.language.isoEnglish
dc.publisherWiley
dc.subjectbeta(2)-adrenergic receptor
dc.subjectbinding affinity
dc.subjectdistinct conformer
dc.subjectdocking
dc.subjectintracellular loop 3
dc.subjectscoring function
dc.titleLigand-binding affinity of alternative conformers of human beta(2)-adrenergic receptor in the presence of intracellular loop 3 (ICL3) and their potential use in virtual screening studies
dc.typeArticle
dc.identifier.startpage883
dc.identifier.endpage899
dc.relation.journalChemical Biology and Drug Design
dc.identifier.issue5
dc.identifier.volume93
dc.identifier.wosWOS:000468814500018
dc.identifier.doi10.1111/cbdd.13478
dc.contributor.khasauthorDilcan, Gonca
dc.contributor.khasauthorAkten, Ebru Demet


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