Lisansüstü Eğitim Enstitüsü

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Browsing Lisansüstü Eğitim Enstitüsü by Department "Enstitüler, Lisansüstü Eğitim Enstitüsü, Biyoloji Ana Bilim Dalı"

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    Master Thesis
    Structure prediction of human DAT and its binding analysis
    (Kadir Has Üniversitesi, 2011) Özal, Tuğba Arzu; Özal, Tuğba Arzu
    Dopamine neurotransmitter and its receptors are crucial in cell signaling process in the brain, which is in charge of information transfer in neurons functioning in the nervous system. Therapeutics used for the treatment of related disorders such as Parkinson?s and schizophrenia would be considerably improved with the availability of the three dimensional (3D) structure of the dopamine transporter (DAT) and of the binding site for dopamine and other ligands.Therefore, in this thesis; I have studied the prospective 3D structures of the neurotransmitter molecules such as human DAT which is predicted from primary amino acid sequence using computational molecular modeling techniques.We have determined the binding sites and relative binding affinities of several ligands with the predicted structures of DAT. These computationally obtained binding affinities and binding sites, i.e. the critical residues of DAT for binding of dopamine and the other ligand molecules, correlate well with experiments. For instance, based on the modeled structures, our calculated binding free energy (?Gbind= -7.4 kcal/mol) for dopamine with DAT is found to be the same as the experimentally observed ?Gbind value of -7.4 kcal/mol.As a conclusion, new 3D structural models of human DAT has been constructed through homology modeling. Two of these human DAT models have been used to determine the binding characteristics between DAT and the ligands by means of computational docking. These kind of computational studies, in which new structural and mechanistic insights were obtained, are expected in future to stimulate, further biochemical and pharmacological studies with much more detailed structures and accordingly, come up with the detailed insights of the working mechanisms of DAT and other homologous transporters.