Ph.D. Theses
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Browsing Ph.D. Theses by Author "Çatak, Şaron."
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Item Assessing protein - ligand binding modes, novel drug skeleton candidates for PDE4B and conformational rearrangements of EF-TU in GTP hydrolysis with computational tools(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2017., 2017.) Çifci, Gülşah.; Çatak, Şaron.; Aviyente, Viktorya.In the first part of this dissertation, computer-aided drug design approaches, structurebased methodologies such as docking, molecular dynamics simulations and Gibbs free energy calculations with Molecular Mechanics-Generalized Born/Surface Area (MMGB/SA) and ligand-based drug design methodologies like pharmacophore modeling are used to propose novel inhibitors for Phosphodiesterase4B (PDE4B) inhibitors. Virtual screening based on structure-based pharmacophore models has been performed for PDE4B inhibitors. The free energy of binding (ΔGbinding) as the total average of 40 independent simulations of each PDE4B inhibitors has been calculated with the MM-GB/SA method. The linear correlation between half maximal inhibitory concentration (IC50) and MM-GB/SA results have been analyzed with the linear dependency between binding affinity (Ki) and IC50, assuming that Michaelis-Menten constant (Km), substrate concentrations [S], and experimental conditions are similar. In the second part of this dissertation, the role of important amino acids in GTPase activity of EF-Tu-GTP for different organisms (Thermos-Aquaticus (T.aquaticus) and Escheria Coli (E.coli) complex have been determined by the aid of molecular dynamics (MD) simulations. The study has been carried out by comparing the experimental results with the results of the MD simulations. The conformational changes during the GTP hydrolysis in the Elongation factor-thermo unstable (EF-Tu) is explained with MD simulations.Item Elucidation of the deamidation mechanism of asparaginyl residues in peptides and proteins(Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2008., 2008.) Çatak, Şaron.; Aviyente, Viktorya.; Ruiz-Lopez, Manuel F.; Monard, Gérald.Demidation of proteins is a topic of wide interest that has been subject to experimental and theoretical studies. Deamidation is a nonenzymatic and spontaneous process that converta asparagine conformational changes in proteins and has been associated with protein degradation and ageing. In this study, certain mechanistic aspects of this process have been investigated and many insights have been attained on potential mechanisms leading to deamidation. These mechanisms and their energetics have been presented in detail. Another potential fate of aparagine residues, backbone cleavage, has been introduced and compared with the deamidation mechanism. Finally, attempts to understand the effect of neighboring residues on Asn deamidation have been elaborated and several ideas for future work n-have benn outlined.Item Molecular modeling of Bcl-xL post-translational modifications and of keteniminium salts(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022., 2022) Tanrıver, Gamze.; Çatak, Şaron.; Monard, Gérald.Computational chemistry plays an important role in deciphering the structural proper ties of systems by using different approaches, such as quantum mechanics (QM) and molecular mechanics (MM) and gives insight by mimicking their dynamic environments. This dissertation contains two main topics, namely investigation of Bcl-xL deamidation via molec ular dynamics (MD) simulations and investigation of keteniminium salts via QM methods. Investigation of post-translational modifications (PTMs) is important to understand their role on the structure and function of proteins. Deamidation, one of the PTMs is a crucial switch used for regulating the biological function of anti-apoptotic Bcl-xL. In the first part of the thesis, deamidation-induced conformational changes in Bcl-xL were explored to gain insight into its loss of function by performing MD simulations. MD outcomes suggest that deamidation allosterically causes remarkable changes in conformation, interaction, and dynamics of Bcl-xL and conceivably impair its function. This study will provide a unique perspective on the underlying mechanism of Bcl-xL deamidation-induced cell death. Keteniminium salts (KIs), nitrogen analogues of ketenes are widely used intermediates for the synthesis of various organic substances due to their higher electrophilicity, reactivity and regioselectivity. In the second part of the thesis, KIs were scrutinized, from their forma tion mechanisms to their involvement in organic reactions, by means of a DFT study. Exper imentally observed reactivity differences in the [2 + 2] cycloaddition and electrocyclization reactions were rationalized via a range of different analysis techniques. The outcomes of this study are expected to contribute to the understanding of the formation mechanism as well as the reactivity differences of keteniminium salts and aid synthetic applications.Item Static and dynamic simulations of photoprocesses in organic phosphorescent and thermally activated delayed fluorescent materials(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2023., 2023) Ulukan, Pelin.; Çatak, Şaron.The development of organic phosphorescent and thermally activated delayed fluorescence (TADF) emitters have emerged as potential candidates for high efficiency organic light-emitting diodes (OLEDs). The common design strategy of both organic phosphorescent and thermally activated emitters is their purely organic structures which provides an opportunity to develop environmentally friendly, low-cost devices with high device efficiencies. Investigation of working mechanisms and design strategies of all electronic devices is important to develop high efficiency technologies. In organic phosphorescent materials, device efficiencies have been increased with the radiative decay observed from the T1 to S0 state. On the other hand, efficiency of TADF materials is mainly controlled by the reverse intersystem crossing (RISC) between T1 and S1 states which leads to the harvesting of generated triplet excitons. In this thesis, experimentally synthesized TADF and room temperature organic phosphorescence materials (oRTP) with various structural properties were modeled to investigate the photophysical processes in their working mechanisms. In the first part, a general benchmark study has been performed on a wide range of TADF emitters with various structural properties. The purpose of this general study was exploring the well performing computational protocol for further, more specific theoretical analyses. In the second and third part of this thesis, boron-based and sulfone-based TADF emitters were analyzed in detail and the role of boron and sulfone containing acceptor moieties on RISC efficiency have been explored. These studies provide a unique perspective on the underlying mechanism of photoprocesses in TADF devices.