Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://gcris.khas.edu.tr/handle/20.500.12469/46

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Citation Count: 12
Blind Dockings of Benzothiazoles To Multiple Receptor Conformations of Triosephosphate Isomerase From Trypanosoma Cruzi and Human
(Wiley-VCH Verlag GmbH, 2011) Kurkcuoglu, Zeynep; Ural, Gulgun; Akten, Ebru Demet; Doruker, Pemra
We aim to uncover the binding modes of benzothiazoles which have been reported as specific inhibitors of triosephosphate isomerase from the parasite Trypanosoma cruzi (TcTIM) by performing blind dockings on both TcTIM and human TIM (hTIM). Detailed analysis of binding sites and specific interactions are carried out based on ensemble dockings to multiple receptor conformers obtained from molecular dynamics simulations. In TcTIM dimer dockings the inhibitors preferentially bind to the tunnel-shaped cavity formed at the interface of the subunits whereas non-inhibitors mostly choose other sites. In contrast TcTIM monomer binding interface and hTIM dimer interface do not present a specific binding site for the inhibitors. These findings point to the importance of the tunnel and of the dimeric form for inhibition of TcTIM. Specific interactions of the inhibitors and their sulfonate-free derivatives with the receptor residues indicate the significance of sulfonate group for binding affinity and positioning on the TcTIM dimer interface. One of the inhibitors also binds to the active site which may explain its relatively higher inhibition effect on hTIM.
Citation Count: 18
Carboxylic Acid Derivatives Display Potential Selectivity for Human Histone Deacetylase 6: Structure-Based Virtual Screening Molecular Docking and Dynamics Simulation Studies
(Elsevier Science, 2018) Uba, Abdullahi Ibrahim; Yelekçi, Kemal
Human histone deacetylase 6 (HDAC6) has been shown to play a major role in oncogenic cell transformation via deacetylation of alpha-tubulin making it a viable target of anticancer drug design and development. The crystal structure of HDAC6 catalytic domain 2 has been recently made available providing avenues for structure-based drug design campaign. Here in our continuous effort to identify potentially selective HDAC6 inhibitors structure-based virtual screening of similar to 72 461 compounds was carried out using Autodock Vina. The top 100 compounds with calculated Delta G < -10 kcal/mol were manually inspected for binding mode orientation. Furthermore the top 20 compounds with reasonable binding modes were evaluated for selectivity by further docking against HDAC6 and HDAC7 using Autodock4. Four compounds with a carboxylic fragment displayed potential selectivity for HDAC6 over HDAC7 and were found to have good druglike and ADMET properties. Their docking complexes were then submitted to 10 ns-molecular dynamics (MD) simulation using nanoscale MD (NAMD) software to examine the stability of ligand binding modes. These predicted inhibitors remained bound to HDAC6 in the presence of water and ions and the root-mean-square deviation (RMSD) radius of gyration (Rg) and nonbond distance (protein-ligand) profiles suggested that they might be stable over time of the simulation. This study may provide scaffolds for further lead optimization towards the design of HDAC6 inhibitors with improved selectivity. (C) 2018 Elsevier Ltd. All rights reserved.
Citation Count: 2
Characterization of Mwcnt-Tio2 Qps and Tio2 Qds in Self-Assembled Films
(Elsevier, 2017) Akkaya Arier, Ümit Özlem; Uysal, Bengü Özuğur
In this study the solution which includes TiO2 quantum dots (QDs) was mixed with the multi-wall carbon nanotubes (MWCNTs) to prepare MWCNT-TiO2 QDs composite films. The effect of microstructures on the structural and optical properties of MWCNT-TiO2 QDs composite films was evaluated. The activation energy for crystallite growth of TiO2 QDs which are produced in brookite phases was calculated as 20.3 kJ/mol. The properties of MWCNT-TiO2 QDs composite films were characterized by X-ray diffraction (XRD) scanning electron microscopy (SEM) atomic force microscopy (AFM) and ultraviolet-visible absorption spectroscopy (UV-vis). (C) 2017 Elsevier GmbH. All rights reserved.
Citation Count: 0
Comp 297-Experimental and Molecular Docking Simulation Studies of Histone Deacetylases (hdacs) Enzyme Inhibitors
(Amer Chemical Soc, 2007) Yelekçi, Kemal; Bora, Gamze; Dayangaç-Erden, Didem; Ayhan, Peruze; Dalkara, Sevim; Demir, Ayhan S.; Erdem-Yurter, Hayat
[Abstract Not Available]
Citation Count: 21
Conductivity Percolation of Carbon Nanotubes (cnt) in Polystyrene (ps) Latex Film
(Canadian Science Publishing Nrc Research Press, 2010) Uğur, Şaziye; Yargı, Önder; Pekcan, Önder
In this study the effect of multiwalled carbon nanotubes (MWNT) on film formation behaviour and electrical conductivity properties of polystrene (PS) latex film was investigated by using the photon transmission technique and electrical conductivity measurements. Films were prepared by mixing PS latex with different amounts of MWNTs varying in the range between 0 and 20 wt%. After drying MWNT content films were separately annealed above the glass transition temperature (T-g) of PS ranging from 100 to 270 degrees C for 10 min. To monitor film formation behavior of PS-MWNT composites transmitted light intensity I-tr was measured after each annealing step. The surface conductivity of annealed films at 170 degrees C was measured and found to increase dramatically above a certain fraction of MWNT (4 wt%) following the percolation theory. This fraction was defined as the percolation threshold of conductivity R-c. The conductivity scales with the mass fraction of MWNT as a power law with exponent 2.27 which is extremely close to the value of 2.0 predicted by percolation theory. In addition the increase in I-tr during annealing was explained by void closure and interdiffusion processes. Film formation stages were modeled and the corresponding activation energies were measured.
Citation Count: 2
Corrected Panel-Reactive Antibody Positivity Rates for Hypersensitized Patients in Turkish Population With Calculated Panel-Reactive Antibody Software
(Elsevier Science Inc, 2017) Karadeniz, Sedat Tanju; Akgül, Sebahat Usta; Öğret, Yeliz; Çiftçi, Hayriye Şentürk; Bayraktar, Adem; Bakkaloğlu, Hüseyin; Çalışkan, Yaşar Kerem; Yelekçi, Kemal; Türkmen, Aydin; Aydın, Ali Emin; Oğuz, Fatma Savran; Çarin, Mahmut Nezih; Aydın, Filiz
however the rate was 86.2% using the cPRA. Discussion. cPRA shows the rate of the rejected donors according to all unacceptable antigens. The need for a list of unacceptable antigens in place of the PRA positivity rate is a real change in the sensitization-dependent calculation as cPRA positivity rate. Conclusion. In principal implementation of cPRA will encourage many centers and laboratories to adopt a standard measurement of sensitization in Turkey. It will increase the chances of better donor match particularly for hypersensitized patients by the creation of an unacceptable mismatch program using cPRA software.
Citation Count: 5
Design, Synthesis and Hmao Inhibitory Screening of Novel 2-Pyrazoline Analogues
(Bentham Science Publ Ltd, 2017) Evranos-Aksöz, Begüm; Uçar, Gülberk; Yelekçi, Kemal
Aim and Objective: MAO inhibitors have a significant effect on the nervous system since they act in regulation of neurotransmitter concentrations. Neurotransmitter levels are critical for a healthy nervous system. MAO inhibitors can be used in the treatment of neurological disorders such as depression, Parkinson's disease and Alzheimer's disease, as the increase or decrease of some neurotransmitter concentrations is associated with these neurological disorders. This study was conducted to discover new and active MAO inhibitor drug candidates. Materials and Methods: New pyrazoline derivatives have been designed with the molecular docking approach and interactions of our compounds with the MAO enzyme have been investigated using the Autodock 4.2 program. The designed pyrazoline derivative compounds were synthesized by the reaction of the chalcones and hydrazides in ethanol. hMAO inhibitory activities of the newly synthesized compounds were investigated by fluorimetric method. In vitro cytotoxicity of five most potent inhibitors were tested in HepG2 cells. Results: (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5i) and (3-(2-hydroxy-4-methoxy phenyl)-5-p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone (5l) inhibited hMAO-A more potently than moclobemide (Ki values are 0.004 +/- 0.001 and 0.005 +/- 0.001, respectively). The same two compounds, 5i and 5l, inhibited hMAO-A more selectively than moclobemide (SI values are 5.55x10(-5) and 0.003, respectively). Both of these compounds were found non toxic at 1 mu M, 5 mu M and 25 mu M concentrations. Conclusion: Two of the newly synthesized compounds, (3-(5-bromo-2-hydroxyphenyl)-5-(4-methoxyphenyl)- 4,5-dihydropyrazol-1-yl)(phenyl) methanone and (3-(2-hydroxy-4-methoxy phenyl)5- p-tolyl-4,5-dihydropyrazol-1-yl)(phenyl) methanone were found to be promising MAO-A inhibitors due to their high inhibitory potency, high selectivity and low toxicity.
Citation Count: 5
Discovery of High Affinity Ligands for Beta(2)-Adrenergic Receptor Through Pharmacophore-Based High-Throughput Virtual Screening and Docking
(Elsevier Science Inc, 2014) Yakar, Rüya; Akten, Ebru Demet
Novel high affinity compounds for human beta(2)-adrenergic receptor (beta(2)-AR) were searched among the clean drug-like subset of ZINC database consisting of 9928465 molecules that satisfy the Lipinski's rule of five. The screening protocol consisted of a high-throughput pharmacophore screening followed by an extensive amount of docking and rescoring. The pharmacophore model was composed of key features shared by all five inactive states of beta(2)-AR in complex with inverse agonists and antagonists. To test the discriminatory power of the pharmacophore model a small-scale screening was initially performed on a database consisting of 117 compounds of which 53 antagonists were taken as active inhibitors and 64 agonists as inactive inhibitors. Accordingly 7.3% of the ZINC database subset (729413 compounds) satisfied the pharmacophore requirements along with 44 antagonists and 17 agonists. Afterwards all these hit compounds were docked to the inactive apo form of the receptor using various docking and scoring protocols. Following each docking experiment the best pose was further evaluated based on the existence of key residues for antagonist binding in its vicinity. After final evaluations based on the human intestinal absorption (HIA) and the blood brain barrier (BBB) penetration properties 62 hit compounds have been clustered based on their structural similarity and as a result four scaffolds were revealed. Two of these scaffolds were also observed in three high affinity compounds with experimentally known K-i values. Moreover novel chemical compounds with distinct structures have been determined as potential beta(2)-AR drug candidates. (C) 2014 Elsevier Inc. All rights reserved.
Citation Count: 0
Docking-Based Virtual Screening for Potential Activity Against Bacterial Pyruvate Kinase
(Springer, 2017) Ergün, Çağla; Akten, Ebru Demet; Doruker, Pemra
[Abstract Not Available]
Citation Count: 0
Effect of Content and Temperature on the Phase Transitions of Polymer Composites Doped by Kappa Carrageenan and Alginate
(Elsevier Academic Press Inc, 2016) Evingür, Gülşen Akın; Pekcan, Önder
[Abstract Not Available]
Citation Count: 6
The Effect of Surfaces on The Orientational Properties and Phase Transitions Peculiarities of a Nonpolar Smectogen
(World Scientific Publ Co Pte Ltd, 2010) Yıldız, Sevtap; Zayim, Esra Ozkan; Pekcan, Önder; Özbek, Haluk
The effect of thin films on the orientational and optical properties of nonpolar monolayer smectogen 4-butoxyphenyl-4'-decyloxybenzoate ((10) over barO (4) over bar) liquid crystal has been studied by polarizing microscopy and high-resolution photon transmission method. The uniform planar textures of (10) over barO (4) over bar on the surfaces coated with WO3 VO2 and WO3-VO2 mixture thin films have been obtained. No significant shifts in the phase transition temperatures to lower values under the influence of the surfaces have been observed. We have also presented the new experimental data on the critical behavior of the layer compression modulus B near the nematic-smectic A transition. It was observed that the data in the vicinity of the transition can be described by a power law expression after the introduction of a first-order correction-to-scaling term within the limit of experimental error. The resulting critical exponent was found to be 0.34 -/+ 0.01 which is good agreement with the previously reported values for other investigated compounds in literature.
Citation Count: 4
Effects of Precursor Parameters on the Optical and Electrical Properties of Azo Nano-Composite Films
(Elsevier GMBH Urban & Fischer Verlag, 2016) Akkaya Arier, Ümit Özlem; Uysal, Bengü Özuğur
Al doped ZnO (AZO) nano-composite films were synthesized on glass substrates with the sol gel spin coating method at the room temperature. The activation energy of AZO nano-composite films was calculated to be 49 kj/mol for the particles growth. The electrical structural and optical properties of AZO films were determined by changing ZnO:water and ZnO:Al ratios. ZnO:water and ZnO:Al ratios play an important role in controlling the electrical conductivity of the AZO nano-composite films. The optimum doping ratio of Al was found to be 2% in terms of the lowest resistivity and above 2% Al-doping concentration the surface resistivity of AZO nano-composite films starts to increase. The optical highest transmittance of the films of 86% in visible region and low surface resistivity of 70 Omega/square can be obtained for the optimum doping ratio of Al. (C) 2016 Elsevier GmbH. All rights reserved.
Citation Count: 15
Electrical and Optical Percolations in Pmma/Gnp Composite Films
(Taylor & Francis Ltd, 2018) Arda, Ertan; Mergen, Omer Bahadir; Pekcan, Önder
Effects of graphene nanoplatelet (GNP) addition on the electrical conductivity and optical absorbance of poly(methyl methacrylate)/graphene nanoplatelet (PMMA/GNP) composite films were studied. Optical absorbance and two point probe resistivity techniques were used to determine the variations of the optical and electrical properties of the composites respectively. Absorbance intensity A and surface resistivity R-s of the composite films were monitored as a function of GNP mass fraction (M) at room temperature. Absorbance intensity values of the composites were increased and surface resistivity values were decreased by increasing the content of GNP in the composite. Electrical and optical percolation thresholds of composite films were determined as M-sigma = 27.5 wt.% and M-op = 26.6 wt.% respectively. The conductivity and the optical results were attributed to the classical and site percolation theories respectively. Optical ((op)) and electrical ((sigma)) critical exponents were calculated as 0.40 and 1.71 respectively.
Citation Count: 4
The Electrochromic Performances of Single Phase Vo2 Nanoparticled Films
(Elsevier Science SA, 2016) Akkaya Arier, Ümit Özlem; Uysal, Bengü Özuğur
In the present work pure phase vanadium oxide VO2 nanoparticled films were synthesized using acetate based sol-gel precursors. The effect of the water: Vanadyl acetylacetonate ratio on electrochemical and structural properties of nanostructured vanadium oxide films was examined. The X-ray diffraction studies indicated that very strong crystallization of the VO2 monoclinic phase occurred for the as-deposited films at the annealing temperature of 500 degrees C. According to the atomic force microscopy and scanning electron microscopy measurements the size and morphology of the granular structured film depend on the water: Vanadyl acetylacetonate ratio. I-V curve spectra were used to compute several characteristics of the films coated on indium tin oxide substrates such as the optical density color efficiency and diffusion coefficient. Even though water: Vanadyl acetylacetonate ratio of 0.1 is expected to give the highest color efficiency value (33 cm(2)/C) higher diffusion coefficient (3.15 x 10(-12) cm(2)/s) is observed in the ratio of 0.01. As a result the correlation between the ratios and electrochromic properties of the films was established. (C) 2016 Elsevier B.V. All rights reserved.
Citation Count: 0
Epitope Based Hla Matching by Using Antibody Reactivity With High Resolution Allele Typing and Hlamatchmaker Algorithm Based Software
(Wiley, 2017) Karadeniz, Sedat Tanju; Akgül, Sebahat Usta; Çiftçi, Hayriye Şentürk; Öğret, Yeliz; Oğuz, Fatma; Yelekçi, Kemal; Aydın, Filiz
[Abstract Not Available]
Citation Count: 12
Examining the Stability of Binding Modes of the Co-Crystallized Inhibitors of Human Hdac8 by Molecular Dynamics Simulation
(Taylor & Francis Inc, 2019) Uba, Abdullahi Ibrahim; Weako, Jackson; Keskin, Özlem; Gürsoy, Attila; Yelekçi, Kemal
Histone deacetylase (HDAC) 8 has been implicated as a potential therapeutic target in a variety of cancers neurodegenerative disorders metabolic dysregulation and autoimmune and inflammatory diseases. Several nonselective HDAC inhibitors have been co-crystallized with HDAC8. Molecular dynamics (MD) studies may yield valuable information on the structural stabilities of the complexes over time as determined by various pharmacophore features of the co-crystallized inhibitors. Here using 11 unmodified X-ray crystal structures of human HDAC8 (complexes) structure-based pharmacophore models were built and clustered based on distance - a function of the number of common pharmacophore features and the root-mean-squared displacement between the matching features. Based on this information a total of seven complexes (1T64 1W22 3RQD 3SFF 3F0R 5VI6 and 5FCW) were submitted to unrestrained 50 ns-MD simulations using nanoscale MD (NAMD) software. 1T64 (HDAC8 in complex with TSA) was found to show the highest stability over time presumably because of the TSA's ability to span HDAC8 catalytic channel and form a strong ionic interaction with zinc metal ion. Other stable complexes were 1W22 3SFF 3F0R and 5FCW. However 3RQD and 5VI6 showed relative instability over 50 ns time period. This may be attributed to bulkiness of the capping groups of both largazole thiol and trapoxin A making them unable to fit well into the active site of HDAC8. They rather formed steric clashes with residues on loop regions near the entrance to the channel. Thus 1T64 and similar crystal structures may be good candidates for HDAC8 structural dynamics studies and inhibitor design. Communicated by Ramaswamy H. Sarma
Citation Count: 0
Fluorescence Study of Effect of Particle Size in Ps Latex/Al2o3 Nanocomposite Films
(MANEY PUBLISHING, 2015) Uğur, Şaziye; Sunay, M. Selin; Pekcan, Önder
Steady state fluorescence and BioUV-Visible techniques were used to study film formation of polystyrene (PS) latex and Al2O3 composites depending on PS particles size and Al2O3 content. Two film series (SmPS/Al2O3 and LgPS/Al2O3) were prepared covering PS sphere (SmPS: 203 nm
Citation Count: 0
Fluorescence Study of Film Formation From Ps Latex-Tio2 Composites: Effects of Tio2 Content Film Thickness and Particle Size
(Amer Scientific Publishers, 2015) Ugur, Saziye; Sunay, M. Selin; Pekcan, Önder
Steady-state fluorescence (SSF) technique in conjunction with UV-visible (UVV) technique atomic force microscope (AFM) and scanning electron microscope (SEM) is used for studying film formation from TiO2 covered polystyrene (PS) latex particles. The effects of TiO2 content film thickness and PS particle size on film formation and structure properties of PS/TiO2 composites are studied. For this purpose in the first part two different sets of PS films with thicknesses of 5 and 20 mu m were prepared from pyrene-(P-) labeled PS particles (320 nm) and covered with various layers of TiO2 with the use of dip-coating method. These films were then annealed at elevated temperatures above glass transition temperature (T-g) of PS in the range of 100-280 degrees C. Fluorescence emission intensity I-p from P and transmitted light intensity I-tr were measured after each annealing step to monitor the stages of film formation. The results show that film formation from PS latexes occurs on the top surface of PS/TiO2 composites and thus develop independent from TiO2 content for both film sets. However the surface morphology of the films was found to vary with both TiO2 content and film thickness. After removal of PS thin films provide a quite ordered porous structure while thick films show nonporous structure. In the second Part two film series were prepared from PS particles with diameters of 203 nm (SmPS) and 382 nm (LgPS) covered with different layers of TiO2 and annealed at elevated temperatures. Results reveal that SmPS/TiO2 films undergo complete film formation independent of the TiO2 content. However no film formation occurs above a certain TiO2 content in LgPS/TiO2 films. SEM images demonstrate that SmPS/TiO2 films have highly well-ordered microporous structures with increasing TiO2 content after extraction of PS polymer whereas LgPS/TiO2 composites show no porous structure for high TiO2 content. Our experiments also show that porous TiO2 films with different sizes could successfully be prepared with this technique.
Citation Count: 0
Fluorescence Technique for Monitoring Swelling of Paam-Kappa Gel Composites
(Shaker Publishing, 2009) Evingür, Gülşen Akin; Aktaş, Demet Kaya; Pekcan, Önder
Steady-state fluorescence (SSF) technique was employed for studying swelling of polyacrylamide (PAAm) gels with various content of kappa- carrageenan. Disc shaped composite gels were prepared by free-radical cross/inking copolymerization of acrylamide (AAm) with various amounts of kappa-carrageenan (kappa C) using N N'- methylenebis (acrylamide) (BIS) as crosslinker in the presence of ammonium persulfate (APS) initiator. Pyranine was introduced as a fluorescence probe. Fluorescence intensity of pyranine was monitored during in situ swelling processes of composite gels. It was observed that fluorescence intensity values decreased as swelling is proceeded. The Li-Tanaka equation was used to determine the swelling time constants tau and cooperative diffusion coefficients D from intensity variations during the swelling processes. It was shown that tau decreased and D increased as the kappa C content in the composites are increased.
Citation Count: 5
Fractal Dimensions of Kappa-Carrageenan Gels During Gelation and Swelling
(Taylor & Francis Inc, 2018) Kara, Selim; Arda, Ertan; Pekcan, Önder
A photon scattering technique for research on the sol-gel and gel-sol transitions in kappa-carrageenan-water systems with various carrageenan contents (CC) was utilized for characterizing the fractal dimensions during gelation and swelling. It was observed that the scattered photon intensity I-sc increased at all temperatures with an increase in the CC when I-sc was monitored against temperature. Additionally the sol-gel transition temperatures were found to be much lower than the gel-sol transition temperatures causing hysteresis of the phase transition loops. I-sc increased with an increase in CC at all test temperatures which is attributed to the formation of a fractal-like carrageenan gel. After drying the gels were used in swelling experiments where the gels were immersed in water at room temperature reswelling to the original structure. It was observed that I-sc from the carrageenan gels increased as the CC was increased. The fractal dimension d during gelation was found to increase as the gelation temperature was increased. On the other hand the d values during swelling decreased as the swelling time was increased.

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