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dc.contributor.authorEvenseth, Linn
dc.contributor.authorWarszycki, Dawid
dc.contributor.authorBojarski, Andrzej J
dc.contributor.authorGabrielsen, Mari
dc.contributor.authorSylte, Ingebrigt
dc.date.accessioned2019-08-14T09:02:09Z
dc.date.available2019-08-14T09:02:09Z
dc.date.issued2019-03-07
dc.description.abstractThe GABA<sub>B</sub> receptor (GABA<sub>B</sub>-R) is a heterodimeric class C G protein-coupled receptor comprised of the GABA<sub>B1a/b</sub> and GABA<sub>B2</sub> subunits. The endogenous orthosteric agonist γ-amino-butyric acid (GABA) binds within the extracellular Venus flytrap (VFT) domain of the GABA<sub>B1a/b</sub> subunit. The receptor is associated with numerous neurological and neuropsychiatric disorders including learning and memory deficits, depression and anxiety, addiction and epilepsy, and is an interesting target for new drug development. Ligand- and structure-based virtual screening (VS) are used to identify hits in preclinical drug discovery. In the present study, we have evaluated classical ligand-based in silico methods, fingerprinting and pharmacophore mapping and structure-based in silico methods, structure-based pharmacophores, docking and scoring, and linear interaction approximation (LIA) for their aptitude to identify orthosteric GABA<sub>B</sub>-R compounds. Our results show that the limited number of active compounds and their high structural similarity complicate the use of ligand-based methods. However, by combining ligand-based methods with different structure-based methods active compounds were identified in front of DUDE-E decoys and the number of false positives was reduced, indicating that novel orthosteric GABA<sub>B</sub>-R compounds may be identified by a combination of ligand-based and structure-based in silico methods.en_US
dc.description.sponsorshipPolish-Norwegian Research Program operated by the Polish National Centre for Research and Development under the Norwegian Financial Mechanism in the frame of the project PLATFORMex <p> <p>Northern Norway Health Authorities (HelseNord) Polish National Centre for Research and Developmenten_US
dc.descriptionSource at <a href=https://doi.org/10.3390/molecules24050935>https://doi.org/10.3390/molecules24050935. </a>en_US
dc.identifier.citationEvenseth, L.M., Warszycki, D., Bojarski, A.J., Gabrielsen, M. & Sylte, I. (2019). In Silico Methods for the Discovery of Orthosteric GABA<sub>B</sub> Receptor Compounds. <i>Molecules, 25</i>(5), 935. https://doi.org/10.3390/molecules24050935en_US
dc.identifier.cristinIDFRIDAID 1714696
dc.identifier.doi10.3390/molecules24050935
dc.identifier.issn1420-3049
dc.identifier.urihttps://hdl.handle.net/10037/15911
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.ispartofEvenseth, L.S.M. (2019). Ligand binding and dynamics of the GABA<sub>B</sub> receptor Venus flytrap domain. (Doctoral thesis). <a href=https://hdl.handle.net/10037/17041>https://hdl.handle.net/10037/17041</a>.
dc.relation.journalMolecules
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectGABAB receptoren_US
dc.subjectorthosteric binding siteen_US
dc.subjectvirtual screeningen_US
dc.subjectligand-based screeningen_US
dc.subjectstructure-based screeningen_US
dc.titleIn Silico Methods for the Discovery of Orthosteric GABAB Receptor Compoundsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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