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dc.contributor.advisorKristiansen, Kurt
dc.contributor.advisorSylte, Ingebrigt
dc.contributor.authorMilicevic, Dusan
dc.date.accessioned2016-07-27T08:57:14Z
dc.date.available2016-07-27T08:57:14Z
dc.date.issued2016-05-12
dc.description.abstractThe serotonin (5-hydroxytryptamine, 5-HT) receptors and transporter are in the serotonergic neurotransmission system, and believed to have a major role in pathology of depression. They are of pharmacological importance, being targeted by many nowadays antidepressants. It is therefore of great interest to understand their structural and functional properties for development of future drugs. There is generally little knowledge today about the effects of environmental toxicants on the human brain. If the exogenous compounds interact with the serotonin receptors and transporter, they may interfere with the serotonergic neurotransmission in the brain and interfere with the effects of the CNS drugs. Homology modelling is an in silico method used for prediction of the 3D structure of structurally unknown proteins. Models of serotonergic receptors (5-HT1A, 5-HT2A, 5-HT2C) were constructed by the homology approach with known structures in the PDB. The newly released X-ray crystal structures of the human serotonin transporter (SERT) were also imported from the PDB and optimized with molecular modelling techniques. Molecular docking was utilized to predict putative harmful effects and drug interactions of the toxicants in the Tox21 database with these protein targets. Many toxic compounds were predicted to interact with serotonergic receptors and the SERT and many of these had physiochemical properties that suggest that they may act in the CNS. Detailed interaction analysis of the selected compounds of serotonergic receptors and the SERT indicated that besides the crucial interaction with an aspartic acid, aromatic interactions with phenylalanine residues are also very important. The obtained high CNS MPO scores and similar Glide scores between the known high affinity binders and toxicants could suggest harmful effects and drug interactions in serotonergic system of the CNS.en_US
dc.identifier.urihttps://hdl.handle.net/10037/9492
dc.identifier.urnURN:NBN:no-uit_munin_9050
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccess
dc.rights.holderCopyright 2016 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/3.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)en_US
dc.subject.courseIDFAR-3911
dc.subjectHomology modellingen_US
dc.subjectComputational scienceen_US
dc.subjectPharmacologyen_US
dc.subjectMedicinal chemistryen_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.titleModelling of serotonergic receptors and molecular optimization of X-ray crystal structures of serotonin transporter and their interactions with exogenous compoundsen_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0)
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