Ligand-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.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.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
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.en_US]
dc.identifier.citation8
dc.identifier.doi10.1111/cbdd.13478en_US
dc.identifier.endpage899
dc.identifier.issn1747-0277en_US
dc.identifier.issn1747-0285en_US
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.issue5
dc.identifier.pmid30637937en_US
dc.identifier.scopus2-s2.0-85061485520en_US
dc.identifier.scopusqualityQ2
dc.identifier.startpage883en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/304
dc.identifier.urihttps://doi.org/10.1111/cbdd.13478
dc.identifier.volume93en_US
dc.identifier.wosWOS:000468814500018en_US
dc.identifier.wosqualityN/A
dc.institutionauthorDilcan, Goncaen_US
dc.institutionauthorAkten, Ebru Demeten_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.journalChemical Biology and Drug Designen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectbeta(2)-adrenergic receptoren_US
dc.subjectbinding affinityen_US
dc.subjectdistinct conformeren_US
dc.subjectdockingen_US
dc.subjectintracellular loop 3en_US
dc.subjectscoring functionen_US
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 studiesen_US
dc.typeArticleen_US
dspace.entity.typePublication

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