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IN-VITRO AND IN-SILICO COMPUTATIONAL MODELLING OF THE CANNABINOID TYPE 1 AND SEROTONIN 2A CLASS A G PROTEIN – COUPLED RECEPTORS

dc.contributor.advisorLaprairie, Robert Brad
dc.contributor.committeeMemberAlcorn, Jane
dc.contributor.committeeMemberLuo, Yu
dc.contributor.committeeMemberDobson, Roy
dc.creatorBrandt, Asher Leib
dc.creator.orcid0000-0002-0498-644X
dc.date.accessioned2022-09-16T15:58:00Z
dc.date.available2022-09-16T15:58:00Z
dc.date.copyright2022
dc.date.created2022-08
dc.date.submittedAugust 2022
dc.date.updated2022-09-16T15:58:00Z
dc.description.abstractG protein-coupled receptors (GPCRs) represent one of the most important families of drug targets. Approximately 700 drugs target GPCR’s, which accounts for 35% of FDA approved drugs. The type 1 cannabinoid receptor (CB1R), type 2 cannabinoid receptor (CB2R), and serotonin 2a receptor (5-HT2AR) are 3 GPCRs being intensively studied as new therapeutic targets. These receptors are involved in pain, depression, anxiety, memory impairment, nausea and body temperature. Due to the vast spectrum of conditions these receptors modulate, development of novel drugs to target these receptors is paramount. Specifically, the studies outlined in this thesis explored the structure activity relationship between ligands that bind CB1R, CB2R and 5-HT2AR using both in silico and in vitro methods. In vitro methods were utilized to determine whether novel ligands bound to the receptor using radioligand binding to measure affinity and functional assays to determine whether ligands activated receptor-dependent signaling cascades such as G protein-dependent inhibition of cAMP accumulation and recruitment of βarrestin2. Computational in silico methods were then explored to determine if the in vitro data could be supported. With these in silico methods the precise site(s) of ligand-GPCR interaction could be mapped down to the amino acid residue for precision structure-activity determination. From this interaction a computational proxy for binding affinity was used to measure the strength of the interaction. Looking forward, data compiled in these studies can now be applied to the high-throughput design and assessment of novel CB1R, CB2R, and 5-HT2AR ligands and potential therapeutics.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10388/14180
dc.language.isoen
dc.subjectMolecular Docking, Psychedelics, G protein-coupled receptors
dc.titleIN-VITRO AND IN-SILICO COMPUTATIONAL MODELLING OF THE CANNABINOID TYPE 1 AND SEROTONIN 2A CLASS A G PROTEIN – COUPLED RECEPTORS
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentPharmacy and Nutrition
thesis.degree.disciplinePharmacology
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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