Biyoinformatik ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12469/46

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Citation - WoS: 17
Citation - Scopus: 20
In Silico Design of Novel and Highly Selective Lysine-Specific Histone Demethylase Inhibitors
(Scientific Technical Research Council Turkey-Tubitak, 2011) Akdoğan, Ebru Demet; Erman, Burak; Yelekçi, Kemal
Histone lysine-specific demethylase (LSD1) is involved in a wide range of epigenetic processes and plays important roles in gene silencing DNA transcription DNA replication DNA repair and heterochromatin formation. Its active site shows a resemblance to those of 2 homologous enzymes monamine oxidase A and B (MAO-A and MAO-B.) In the present work starting from suitable scaffolds and generating thousands of structures from them 10 potential inhibitors were obtained with structural and physicochemical properties selectively suitable for inhibiting LSD1. iLib Diverse software was used to generate the diverse structures and 3 docking tools CDOCKER GOLD and AutoDock were used to find the most probable potential inhibitor based on its binding affinity. The dispositions of the candidate molecules within the organism were checked by ADMET_PSA_2D (polar surface area) versus ADMET_AlogP98 (the logarithm of the partition coefficient between n-octanol and water) and their suitability is discussed. The LSD1 inhibition activities of the candidates were compared with the properties of trans-2-phenylcyclopropylamine (tranylcypromine) and 2-(4-methoxy-phenyl) cyclopropylamine which are the 2 known inhibitors of LSD1.
Citation - WoS: 145
Citation - Scopus: 145
Psychological Correlates of Covid-19 Conspiracy Beliefs and Preventive Measures: Evidence From Turkey
(Springer, 2020) Alper, Sinan; Bayrak, Fatih; Yılmaz, Onurcan
COVID-19 pandemic has led to popular conspiracy theories regarding its origins and widespread concern over the level of compliance with preventive measures. In the current preregistered research, we recruited 1088 Turkish participants and investigated (a) individual differences associated with COVID-19 conspiracy beliefs; (2) whether such conspiracy beliefs are related to the level of preventive measures; and (3) other individual differences that might be related to the preventive measures. Higher faith in intuition, uncertainty avoidance, impulsivity, generic conspiracy beliefs, religiosity, and right-wing ideology, and a lower level of cognitive reflection were associated with a higher level of belief in COVID-19 conspiracy theories. There was no association between COVID-19 conspiracy beliefs and preventive measures while perceived risk was positively and impulsivity negatively correlated with preventive measures. We discuss the implications and directions for future research.
Citation - WoS: 7
Citation - Scopus: 6
Investigation of Pst-Mwcnt Concentration on Epoxyacrylate Photopolymerization and Conductivity of Polymer Films
(Elsevier Science SA, 2013) Doğruyol, Zekeriya; Temel, Gökhan; Doğruyol, Sevnur Keskin; Pekcan, Önder; Arsu, Nergis
Photopolymerization kinetics and conductivity changes of epoxyacrylate composites for various loading modified PSt-MWCNT weight fractions changing from 0.0025 to 0.2 wt.% were evaluated by performing photo differential scanning calorimetry (photo-DSC) and four point conductivity measurements. 0.2% PSt-MWCNT additive polymeric films had their electrical conductivity boosted by 6% more than non-additive polymeric films. (C) 2012 Elsevier B.V. All rights reserved.
Citation - WoS: 1
Citation - Scopus: 1
The Role of Pyranine in Characterization of Paam-Kappa C Composites by Using Fluorescence Technique
(Springer/Plenum Publishers, 2011) Evingür, Gülşen Akın; Pekcan, Önder
Polyacrylamide (PAAm) doped by kappa-carrageenan (kappa C) gels were prepared with various amounts of kappa C varying in the range between 0 wt.% and 3 wt.%. Steady-state fluorescence (SSF) technique was employed for studying sol-gel transition and swelling of PAAm-kappa C composite gels which were prepared by free-radical crosslinking copolymerization. Pyranine was introduced as a fluorescence probe. Pyranine molecules start to bind to acrylamide polymer chains upon the initiation of the polymerization thus the spectra of the bonded pyranines shift to the shorter wavelengths. Fluorescence spectra from the bonded pyranines allow one to monitor the sol-gel transition and to test the universality of the sol-gel transition as a function of some kinetic parameters like polymer concentration. Observations around the gel point t (c) for PAAm-kappa C composite gels showed that the gel fraction exponent beta obeyed the percolation result for low kappa C (< 2.0 wt. %) however classical results were produced at higher kappa C (> 2.0 wt.%). On the other hand fluorescence intensity of pyranine was measured during in situ swelling process at various amounts of kappa C and it was observed that fluorescence intensity values decreased as swelling is proceeded. Li-Tanaka equation was used to determine the swelling time constants tau and cooperative diffusion coefficients D.
Citation - WoS: 4
Conductivity Percolation of Carbon Nanotubes in Polyacrylamide Gels
(Intech Europe, 2011) Pekcan, Önder; Evingür, Gülşen Akın
[Abstract Not Available]
Citation - WoS: 13
Citation - Scopus: 13
In Situ Steady State Fluorescence (ssf) Technique To Study Drying of Paam Hydrogels Made of Various Cross-Linker Contents
(Elsevier Science, 2009) Evingür, Gülşen Akın; Aktas, Demet Kaya; Pekcan, Önder
Drying experiments of polyacrylamide (PAAm) gels were performed using steady-state fluorescence (SSF) spectrometer. Pyranine (P) was introduced as a fluorescence probe and intensity of P from various crosslinker content gel samples was monitored. It was observed that the intensity of P increased during the in situ drying processes. Gravimetrical and volumetric experiments were also performed. An empirical model was derived and introduced to determine the desorption coefficient D of water molecules from the drying PAAm gels. It is observed that D increased as the cross-linker content was increased. (c) 2008 Elsevier B.V. All rights reserved.
Citation - WoS: 6
Citation - Scopus: 7
Drying of Polyacrylamide Composite Gels Formed With Various Kappa- Carrageenan Content
(Springer/Plenum Publishers, 2011) Evingür, Gülşen Akın; Pekcan, Önder
Drying of polyacrylamide (PAAm)-kappa-carrageenan (kappa C) composite gels were monitored by using steady-state fluorescence technique. Disc shaped gels were formed from acrylamide (AAm) and N N'- methylenebisacrylamide(Bis) with various kappa- carrageenan (kappa C) contents by free radical crosslinking copolymerization in water. Pyranine (P) was doped as a fluorescence probe and scattered light I (sc) and fluorescence intensities I were monitored during drying of these gels. It is observed that fluorescence intensity of pyranine increased as drying time is increased for all samples. The increase in I was modeled using Stern- Volmer equation and diffusion with moving boundary. It is found that desorption coefficient D decreased as kappa C contents were increased. Supporting gravimetrical and volumetric experiments were also carried out during drying of PAAm- kappa C composite gels.
Citation - WoS: 54
Citation - Scopus: 66
Synthesis Molecular Modeling in Vivo Study and Anticancer Activity of 124-Triazole Containing Hydrazide-Hydrazones Derived From (s)-Naproxen
(Wiley-VCH Verlag GmbH, 2019) Han, Muhammed İhsan; Bekçi, Hatice; Uba, Abdullahi İbrahim; Yıldırım, Yeliz; Karasulu, Ercüment; Cumaoğlu, Ahmet; Karasulu, Hatice Y.; Yelekçi, Kemal; Yılmaz, Ozguer; Küçükgüzel, Şükriye Güniz
A new series of 124-triazole containing hydrazide-hydrazones derived from (S)-naproxen (7a-m) was synthesized in this study. The structures of these compounds were characterized by spectral (Fourier-transform infrared spectroscopy H-1-nuclear magnetic resonance (NMR) C-13-NMR and high-resolution electron ionization mass spectrometry) methods. Furthermore molecular modeling of these compounds was studied on human methionine aminopeptidase-2. All synthesized compounds were screened for anticancer activity against three prostate cancer cell lines (PC3 DU-145 and LNCaP) using the 3-(45-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium colorimetric method. Compound 7a showed the best activity against the PC3 DU-145 and LNCaP cancer cell lines with IC50 values of 26.0 34.5 and 48.8 mu M respectively. Compounds 7b 7k and 7m showed anticancer activity against cancer cell lines PC3 and DU-145 with IC50 values of 43.0 36.5 29.3 mu M and 49.8 49.1 31.6 mu M respectively. Compounds 7f and 7g showed anticancer activity against PC3 cells with IC50 values of 43.4 and 34.5 mu M respectively. To assess the biodistribution in mice of IRDye800 dye-labeled compound 7a or 100 mu M of free dye was injected intravenously into the mice's tail. In vivo images were taken with in vivo imaging system spectrum device at 60 120 180 240 300 and 360 min after injection. At the end of 360 min ex vivo studies were carried out to determine in which organs the dye was accumulated in the urogenital system. Ex vivo studies showed that the accumulation of compound 7a in the prostate is greater than that of the free dye and it is concluded that compound 7a may be promising for the treatment of prostate cancer..
Citation - WoS: 8
Citation - Scopus: 8
Elastic Properties of a Swollen Paam-Nipa Copolymer With Various Nipa Contents
(Taylor & Francis, 2014) Evingür, Gülşen Akin; Pekcan, Önder
Copolymer based on cross-linked polyacrylamide (PAAm) having N-isopropylacrylamide (NIPA) was prepared and their elastic properties were studied as a function of NIPA contents. NIPA content dependency of the shear modulus S of the PAAm-NIPA copolymers due to volume phase transition was measured using tensile testing technique at 30 degrees C. It was observed that its shear modulus and toughness were found to be strongly dependent on NIPA content. It is understood that the shear modulus was found to increase with NIPA contents keeping constant temperature at 30 degrees C. Elastic properties of the PAAm-NIPA copolymers show compositional dependence.
Citation - WoS: 4
Citation - Scopus: 4
Thermal Rearrangement of 2-Acetoxy Theoretical Elucidation of the Mechanism
(Elsevier Science, 2007) Erdem, Safiye Sağ; Uyar, Fahriye; Karahan, Özlem; Yelekçi, Kemal
Bicyclohexenes are believed to be the immediate precursors of aromatic compounds. As a part of the exploratory study of thermal aromatization reactions 266-trimethylbicyclo[3.1.0]hexan-2-ol and its ester derivative 2-acetoxy-266-trimethylbicyclo[3.1.0]hexane were synthesized. Pyrolysis of 2-acetoxy-266-trimethylbicyclo[3.1.0]hexane at 350 degrees C gave 133-trimethyl-14-cyclohexadiene instead of the expected product 266-trimethylbicyclo[3.1.0]hex-2-ene. Computational methods such as PM3 31G]* were employed in order to elucidate the mechanism of this reaction. The Gibbs free energy of activation and the reaction energy were calculated for the proposed polar and biradical mechanisms. The results showed that a two-step mechanism is plausible at 350 degrees C in which the expected product 266-trimetliylbicyclo[3.1.0]hex2-ene is the intermediate. The first step is the 12-elimination of the ester leading to 266-trimethylbicyclo [3. 1. 0]hex-2-ene. The second step is the sigmatropic rearrangement of 266-trimethylbicyclo[3.1.0]hex-2-ene via concerted homodienyl 15-hydrogen shift which is also the rate-determining step. UB3LYP/6-31G* calculations reveal that the cyclopropyl moiety of bicyclo[3.1.0]hex-2-ene can undergo homolytic bond cleavage to give an allylically stabilized biradical intermediate. However the formation of 14-cyclohexadiene from such an intermediate through a biradical transition state involving 12-hydrogen migration does not seem to be plausible. (c) 2007 Elsevier B.V. All rights reserved.
Citation - WoS: 8
Citation - Scopus: 9
Antifungal Screening and in Silico Mechanistic Studies of an In-House Azole Library
(2019) Sarı, Suat; Kart, Didem; Sabuncuoğlu, Suna; Doğan, İnci Selin; Özdemir, Zeynep; Bozbey, İrem; Gencel, Melis; Eşsiz, Şebnem; Reynisson, Jóhannes; Karakurt, Arzu; Saraç, Selma; Dalkara, Sevim
Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.
Citation - WoS: 25
Citation - Scopus: 26
How an Inhibitor Bound To Subunit Interface Alters Triosephosphate Isomerase Dynamics
(Cell Press, 2015) Kürkçüoğlu, Zeynep; Fındık, Doğa; Akdoğan, Ebru Demet; Doruker, Pemra
The tunnel region at triosephosphate isomerase (TIM)'s dimer interface distant from its catalytic site is a target site for certain benzothiazole derivatives that inhibit TIM's catalytic activity in Trypanosoma cruzi the parasite that causes Chagas disease. We performed multiple 100-ns molecular-dynamics (MD) simulations and elastic network modeling (ENM) on both apo and complex structures to shed light on the still unclear inhibitory mechanism of one such inhibitor named bt10. Within the time frame of our MD simulations we observed stabilization of aromatic clusters at the dimer interface and enhancement of intersubunit hydrogen bonds in the presence of bt10 which point to an allosteric effect rather than destabilization of the dimeric structure. The collective dynamics dictated by the topology of TIM is known to facilitate the closure of its catalytic loop over the active site that is critical for substrate entrance and product release. We incorporated the ligand's effect on vibrational dynamics by applying mixed coarse-grained ENM to each one of 54000 MD snapshots. Using this computationally efficient technique we observed altered collective modes and positive shifts in eigenvalues due to the constraining effect of bt10 binding. Accordingly we observed allosteric changes in the catalytic loop's dynamics flexibility and correlations as well as the solvent exposure of catalytic residues. A newly (to our knowledge) introduced technique that performs residue-based ENM scanning of TIM revealed the tunnel region as a key binding site that can alter global dynamics of the enzyme.
Citation - WoS: 1
Citation - Scopus: 2
Group Behaviour in Physical Chemical and Biological Systems
(Indıan Acad Scıences, 2014) Saçlıoğlu, Cihan; Pekcan, Önder; Nanjundiah, Vidyanand
Groups exhibit properties that either are not perceived to exist or perhaps cannot exist at the individual level. Such 'emergent' properties depend on how individuals interact both among themselves and with their surroundings. The world of everyday objects consists of material entities. These are ultimately groups of elementary particles that organize themselves into atoms and molecules occupy space and so on. It turns out that an explanation of even the most commonplace features of this world requires relativistic quantum field theory and the fact that Planck's constant is discrete not zero. Groups of molecules in solution in particular polymers ('sols') can form viscous clusters that behave like elastic solids ('gels'). Sol-gel transitions are examples of cooperative phenomena. Their occurrence is explained by modelling the statistics of inter-unit interactions: the likelihood of either state varies sharply as a critical parameter crosses a threshold value. Group behaviour among cells or organisms is often heritable and therefore can evolve. This permits an additional typically biological explanation for it in terms of reproductive advantage whether of the individual or of the group. There is no general agreement on the appropriate explanatory framework for understanding group-level phenomena in biology.
Citation - WoS: 22
Citation - Scopus: 21
Synthesis Anticancer Activity and Molecular Modeling of Etodolac-Thioether Derivatives as Potent Methionine Aminopeptidase (type Ii) Inhibitors
(Wiley, 2018) Çoruh, Işıl; Çevik, Ozge; Yelekçi, Kemal; Djikic, Teodora; Küçükgüzel, Şükriye Güniz
A series of (RS)-1-{[5-(substituted)sulfanyl-4-substituted-4H-124-triazole-3-yl]methyl}-18-diethyl-1349-tetrahydropyrano[34-b]indoles (5a-v) were designed and synthesized using a five-step synthetic protocol that involves substituted benzyl chlorides and (RS)-5-[(18-diethyl-1349-tetrahydropyrano[34-b]indole-1-yl)methyl]-4-substituted-24-dihydro-3H-124-triazole-3-thiones in the final step. The synthesized derivatives were evaluated for cytotoxicity and anticancer activity in vitro using the MTT (3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide) colorimetric method against VERO HEPG2 (human hepatocellular liver carcinoma) SKOV3 (ovarian carcinoma) MCF7 (human breast adenocarcinoma) PC3 and DU145 (prostate carcinoma) cells at 10(-5)M (10M) for 24h. Compounds 5d and 5h showed the best biological potency against the SKOV3 cancer cell line (IC50=7.22 and 5.10M respectively) and did not display cytotoxicity toward VERO cells compared to etodolac. Compounds 5k 5s and 5v showed the most potent biological activity against the PC3 cancer cell line (IC50=8.18 3.10 and 4.00M respectively) and did not display cytotoxicity. Moreover these compounds were evaluated for caspase-3 -9 and -8 protein expression and activation in the apoptosis pathway for 6 12 and 24h which play a key role in the treatment of cancer. In this study we also investigated the apoptotic mechanism and molecular modeling of compounds 5k and 5v on the methionine aminopeptidase (type II) enzyme active site in order to get insights into the binding mode and energy.
Collective Enhancement of Nuclear State Densities by the Shell Model Monte Carlo Approach
(IOP Publishing Ltd, 2015) Özen, Cem; Alhassid, Yoram; Nakada, Hitoshi
The shell model Monte Carlo (SMMC) approach allows for the microscopic calculation of statistical and collective properties of heavy nuclei using the framework of the configuration-interaction shell model in very large model spaces. We present recent applications of the SMMC method to the calculation of state densities and their collective enhancement factors in rare-earth nuclei.
Citation - WoS: 2
Citation - Scopus: 2
Fractal Features and Structural Morphological Optical Characteristics of Sol-Gel Derived Silica Nanoparticled Thin Films
(Polish Acad Sciences Inst Physics, 2018) Uysal, Bengü Özuğur; Pekcan, Önder
Nanostructured silica films using a simple and effective sol-gel spin coating technique were synthesized and the influence of ammonia/sol ratios on the particle size and thickness of this film was investigated. In addition fractal dimensions of the prepared films were determined using the scattering response technique. The samples were characterized by atomic force microscopy and UV-vis spectroscopy. Comparing optical method and image analysis of atomic force microscopy micrographs the fractal dimension of silica nanoparticled thin films was determined. The fractal dimensions of the films verified by atomic force microscopy analysis were found to be around 2.03 which is very close to the values (2.0358 2.0325 and 2.0335) obtained using optical method. As a result of these findings precise determination of the nanoparticled silica thin films fractal dimension using both optical and surface analysis methods was realized.
Citation - WoS: 1
Citation - Scopus: 1
Exploring Distinct Binding Site Regions of Beta(2)-Adrenergic Receptor Via Coarse-Grained Molecular Dynamics Simulations
(Scientific Technical Research Council Turkey-Tubitak, 2013) Cakan, Sibel; Akdoğan, Ebru Demet
beta(2)-Adrenergic receptor (beta(2)AR) is a G protein-coupled receptor that is highly flexible and able to recognize a wide range of ligands through its conformational variations. Active and inactive conformations revealed by recent crystallographic experiments do not provide a complete dynamic picture of the receptor especially in the binding site. In this study molecular dynamics (MD) simulation through a residue-based coarse-grained model is used as an alternative and efficient method to explore a wider conformational search space. The system was composed of beta(2)AR embedded into a 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane bilayer with surrounding water. A total of 6 mu s of simulation at constant NPT was performed for a system of 6868 coarse-grained beads. The system reached equilibrium at around 0.1 mu s. The overall 3-dimensional structure was well preserved throughout the simulation. Local residue-based fluctuations were in good agreement with fully atomistic MD simulations. Four distinct snapshots were selected and reverse-mapped to all-atom representations with around 65000 atoms. Each reverse-mapped system was later subjected to 100 ns of MD simulation for equilibration. Root mean square deviation clustering analysis yielded distinct receptor conformers for the binding site regions which were suggested to be alternative representations of the binding pocket and thus were proposed as plausible targets in docking-based virtual screening experiments for the discovery of novel antagonists.
Soman as a Wrench in the Works of Human Acetylcholinesterase: Soman Induced Conformational Changes Revealed by Molecular Dynamics Simulations
(Amer Chemical Soc, 2014) Bennion, Brian J.; Eşsiz, Şebnem; Lau, Edmond Y.; Fattebert, Jean-Luc; Emigh, Aiyana; Lightstone, Felice C.
[Abstract Not Available]
Citation - WoS: 2
Citation - Scopus: 3
Mapping the Two-Component Atomic Fermi Gas To the Nuclear Shell-Model
(Springer, 2014) Özen, Cem; Zinner, Nikolaj Thomas
The physics of a two-component cold Fermi gas is now frequently addressed in laboratories. Usually this is done for large samples of tens to hundreds of thousands of particles. However it is now possible to produce few-body systems (1-100 particles) in very tight traps where the shell structure of the external potential becomes important. A system of two-species fermionic cold atoms with an attractive zero-range interaction is analogous to a simple model of nucleus in which neutrons and protons interact only through a residual pairing interaction. In this article we discuss how the problem of a two-component atomic Fermi gas in a tight external trap can be mapped to the nuclear shell-model so that readily available many-body techniques in nuclear physics such as the Shell-Model Monte Carlo (SMMC) method can be directly applied to the study of these systems. We demonstrate an application of the SMMC method by estimating the pairing correlations in a small two-component Fermi system with moderate-to-strong short-range two-body interactions in a three-dimensional harmonic external trapping potential.
Citation - WoS: 49
Citation - Scopus: 53
New Azole Derivatives Showing Antimicrobial Effects and Their Mechanism of Antifungal Activity by Molecular Modeling Studies
(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Doğan, İnci Selin; Saraç, Selma; Sarı, Suat; Kart, Didem; Eşsiz, Şebnem; Vural, İmran; Dalkara, Sevim
Azole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally some of our compounds such as 19 (MIC: 0.25 mu g/mL) were potent against resistant C. glabrata a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. (C) 2017 Elsevier Masson SAS. All rights reserved.

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