Biyoinformatik ve Genetik Bölümü Koleksiyonu

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

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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: 1
Citation - Scopus: 1
Assessing Protein-Ligand Binding Modes With Computational Tools: the Case of Pde4b
(Springer, 2017) Çifii, Gülşah; Aviyente, Viktorya; Akten, Ebru Demet; Monard, Gerald
In a first step in the discovery of novel potent inhibitor structures for the PDE4B family with limited side effects we present a protocol to rank newly designed molecules through the estimation of their IC values. Our protocol is based on reproducing the linear relationship between the logarithm of experimental IC values [(IC)] and their calculated binding free energies (). From 13 known PDE4B inhibitors we show here that (1) binding free energies obtained after a docking process by AutoDock are not accurate enough to reproduce this linear relationship
Citation - WoS: 5
Citation - Scopus: 7
Calculating Level Densities of Heavy Nuclei by the Shell Model Monte Carlo Method
(Academic Press Inc Elsevier Science, 2014) Alhassid, Yoram; Özen, Cem; Nakada, Hitoshi
The microscopic calculation of nuclear level densities in the presence of correlations is a difficult many-body problem. The shell model Monte Carlo method provides a powerful technique to carry out such calculations using the framework of the configuration-interaction shell model in spaces that are many orders of magnitude larger than spaces that can be treated by conventional methods. We present recent applications of the method to the calculation of level densities and their collective enhancement factors in heavy nuclei. The calculated level densities are in close agreement with experimental data.
Citation - WoS: 17
Citation - Scopus: 16
Cation Effect on Slow Release From Alginate Beads: a Fluorescence Study
(Springer/Plenum Publishers, 2014) Kaygusuz, Hakan; Erim, F. Bedia; Pekcan, Önder; Evingür, Gülşen Akin
In this study spherical alginate beads containing pyranine (P-y) as a fluorescence probe were prepared by ionotropic gelation of a sodium alginate solution. The steady state fluorescence technique was used to study pyranine release from the alginate beads crosslinked with calcium barium and aluminum ions respectively. The slow release of P-y was observed with the time drive mode of the spectrophotometer at 512 nm. Fluorescence emission intensity (I-p) from P-y was monitored during the release process and the encapsulation efficiency (EE) of pyranine from the alginate beads was calculated. The Fickian Diffusion model was used to measure the release coefficients D-sl. It was seen that the slow release coefficients of pyranine from the alginate beads crosslinked with Ca2+ Ba2+ and Al3+ ions increased in the following order: D-sl (Al3+)> D-sl (Ca2+)> D-sl (Ba2+). In contrast the initial amount of pyranine and EE into the beads showed the reverse behavior.
Citation - WoS: 33
Citation - Scopus: 33
Cis-Cyclopropylamines as Mechanism-Based Inhibitors of Monoamine Oxidases
(Wiley-Blackwell, 2015) Malcomson, Thomas; Yelekçi, Kemal; Borrello, Maria Teresa; Ganesan, A.; Semina, Elena; De Kimpe, Norbert; Mangelinckx, Sven; Ramsay, Rona R.
Cyclopropylamines inhibitors of monoamine oxidases (MAO) and lysine-specific demethylase (LSD1) provide a useful structural scaffold for the design of mechanism-based inhibitors for treatment of depression and cancer. For new compounds with the less common cis relationship and with an alkoxy substituent at the 2-position of the cyclopropyl ring the apparent affinity determined from docking experiments revealed little difference between the enantiomers. Using the racemate kinetic parameters for the reversible and irreversible inhibition of MAO were determined. No inhibition of LSD1 was observed. For reversible inhibition most compounds gave high IC50 values with MAO A but sub-micromolar values with MAO B. After pre-incubation of the cyclopropylamine with the enzyme the inhibition was irreversible for both MAOA and MAOB and the activity was not restored by dilution. Spectral changes during inactivation of MAOA included bleaching at 456nm and an increased absorbance at 400nm consistent with flavin modification. These derivatives are MAOB-selective irreversible inhibitors that do not show inhibition of LSD1. The best inhibitor was cis-N-benzyl-2-methoxycyclopropylamine with an IC50 of 5nm for MAOB and 170nm for MAOA after 30min pre-incubation. This cis-cyclopropylamine is over 20-fold more effective than tranylcypromine so may be studied as a lead for selective inhibitors of MAOB that do not inhibit LSD1.
Citation - Scopus: 3
Comparison of Cation Effects on Phase Transitions of Kappa and Iota Carrageenan
(European Polymer Federation, 2010) Tari, Özlem; Pekcan, Önder
Phase transitions of kappa and iota carrageenan in KCl NaCl and CaCl2 solutions were separately studied during heating and cooling processes by using fluorescence technique. Scattered light I-SC and fluorescence intensity I was monitored against temperature to determine the critical transition temperatures and exponents. Kappa and iota carrageenans with monovalent (KCl NaCl) salt system presented only coil to double helix (c-h) and double helix to coil (h-c) transitions upon cooling and heating processes respectively. Two transition regions were observed in both heating and cooling of the iota carrageenan in CaCl2 solution while in kappa carrageenan only (c-h) and (h-c) transitions was detected. During heating dimers decompose into double helices by making (d-h) transition. At the high temperature region (h-c) transition takes place. During cooling back transitions repeat themselves. A hysteresis was observed between (h-c) and (c-h) for the kappa and iota carrageenan salt system (except CaCl2) respectively. Dimer to double helix (d-h) and double helix to dimer (h-d) transitions were observed for iota carrageenan in CaCl2 salt. The gel fraction exponent beta was measured and found to be in accord with the classical Flory-Stockmayer Model for both kappa and iota carrageenan salt systems.
Citation - WoS: 6
Citation - Scopus: 6
A Comparison of Fluorescence and Uv-Visible Spectrometry Techniques for Thermal Phase Transitions of Agarose Gels
(Springer, 2015) Arda, Ertan; Kara, Selim; Mergen, Ömer Bahadır; Pekcan, Önder
In this study thermoreversible phase transitions of high (HMP) and low (LMP) melting point agarose gels were investigated by using the UV-vis and fluorescence spectroscopy techniques. Pyranine was added to the aqueous solution of agarose as a fluorescence-probe. Transmitted light (I (tr)) and fluorescence emission (I (fl)) intensities from the gel samples with different agarose concentrations were monitored during the heating (gel-sol) and cooling (sol-gel) processes. For the both techniques gel-sol (T (gs)) and sol-gel (T (sg)) transition temperatures were determined from the first derivatives of the sigmoidal transition paths. It was observed that the critical transition temperatures obtained from UV-vis and fluorescence data slightly increased depending on the agarose type and concentration and those values were found to be in accord with each other. Transition activation energies were determined using the Arrhenius type equation and were found to be strongly correlated with the agarose content in the gel system. The produced gel-sol (Delta E (gs)) and sol-gel (Delta E (sg)) transition energies from the fluorescence data were found to be lower than that of the UV-vis data which was attributed to the temperature-dependent fluorescence quenching effect.
Citation - WoS: 3
Citation - Scopus: 2
Coulomb Corrections in the Lepton-Pair Production in Ultrarelativistic Nuclear Collisions
(Amer Physical Soc., 2005) Güçlu, Mehmet C.; Kovankaya, G.; Yılmaz, Melek
We solve the perturbative electron-positron pair production exactly by calculating the second-order Feynman diagrams. We compare our result with Born methods that include Coulomb corrections. We find that a small-momentum approximation is not adequate to obtain exact Coulomb corrections and higher-order terms should also be included. We also compare the impact parameter dependence cross sections.
Design and Synthesis of Novel 2-Pyrazoline Analogues and Their Hmao Inhibitory Activities
(Wiley-Blackwell, 2015) Uçar, Gülberk; Evranos-Aksoz, Begum; Yabanoglu-Çiftçi, Samiye; Yelekçi, Kemal
[Abstract Not Available]
Citation - WoS: 4
Citation - Scopus: 4
Diffusion Energies of Oxygen Diffusing Into Polystyrene (ps)/Poly (n-Isopropylacrylamide) Composites
(Wiley-Blackwell, 2012) Yargı, Önder; Ugur, Saziye; Pekcan, Önder
Diffusion coefficient of oxygen penetrating into polystyrene (PS) latex/poly (N-isopropylacrylamide) (PNIPAM) microgel composite films were measured using Fluorescence technique. Three different (5 15 and 40wt%) PS content films were prepared from PS/PNIPAM mixtures. Diffusivity of PS/PNIPAM composite films were studied by diffusion measurements which were performed over the temperature range of 24-70 degrees C. Pyrene was used as the fluorescent probe. The diffusion coefficients (D) of oxygen were determined using the SternVolmer fluorescence quenching method combined with Fickian transport and were computed as a function of temperature for each PS content film. The results showed that D values were strongly dependent on both temperature and PS content in the film. Diffusion energies were measured and found to be dependent on the composition of the composite films. Copyright (C) 2011 John Wiley & Sons Ltd.
Citation - WoS: 6
Citation - Scopus: 7
Distinctive Communication Networks in Inactive States of Beta(2)-Adrenergic Receptor: Mutual Information and Entropy Transfer Analysis
(Wiley, 2020) Soğünmez, Nuray; Akten, Ebru Demet
Mutual information and entropy transfer analysis employed on two inactive states of human beta-2 adrenergic receptor (beta(2)-AR) unraveled distinct communication pathways. Previously, a so-called "highly" inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G-protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone-C(alpha)fluctuations was mostly shared between intra- and extra-cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar-polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone-C(alpha)fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.
Citation - WoS: 59
Citation - Scopus: 57
Docking Studies on Monoamine Oxidase-B Inhibitors: Estimation of Inhibition Constants (k-I) of a Series of Experimentally Tested Compounds
(Pergamon-Elsevier Science Ltd, 2005) Toprakçı, Mustafa; Yelekçi, Kemal
Monoamine oxidase (EC1.4.3.4
Citation - Scopus: 23
The Drosophila Fragile X Mental Retardation Protein Participates in the Pirna Pathway
(Company of Biologists Ltd, 2015) Bozzetti, Maria Pia; Specchia, Valeria; Cattenoz, Pierre B.; Laneve, Pietro; Geusa, Annamaria; Şahin, H. Bahar; Di Tommaso, Silvia D.; Friscini, Antonella; Massari, Serafina; Diebold, Celine; Giangrande, Angela
RNA metabolism controls multiple biological processes and a specific class of small RNAs called piRNAs act as genome guardians by silencing the expression of transposons and repetitive sequences in the gonads. Defects in the piRNA pathway affect genome integrity and fertility. The possible implications in physiopathological mechanisms of human diseases have made the piRNA pathway the object of intense investigation and recent work suggests that there is a role for this pathway in somatic processes including synaptic plasticity. The RNA-binding fragile X mental retardation protein (FMRP also known as FMR1) controls translation and its loss triggers the most frequent syndromic form of mental retardation as well as gonadal defects in humans. Here we demonstrate for the first time that germline as well as somatic expression of Drosophila Fmr1 (denoted dFmr1) the Drosophila ortholog of FMRP are necessary in a pathway mediated by piRNAs. Moreover dFmr1 interacts genetically and biochemically with Aubergine an Argonaute protein and a key player in this pathway. Our data provide novel perspectives for understanding the phenotypes observed in Fragile X patients and support the view that piRNAs might be at work in the nervous system. © 2015.
Citation - WoS: 56
Citation - Scopus: 72
Drug Design for Cns Diseases: Polypharmacological Profiling of Compounds Using Cheminformatic, 3d-Qsar and Virtual Screening Methodologies
(Frontiers Media Sa, 2016) Nikolic, Katarina; Mavridis, Lazaros; Djikic, Teodora; Vucicevic, Jelica; Agbaba, Danica; Yelekçi, Kemal; Mitchell, John B. O.
The diverse cerebral mechanisms implicated in Central Nervous System (CNS) diseases together with the heterogeneous and overlapping nature of phenotypes indicated that multitarget strategies may be appropriate for the improved treatment of complex brain diseases. Understanding how the neurotransmitter systems interact is also important in optimizing therapeutic strategies. Pharmacological intervention on one target will often influence another one, such as the well-established serotonin-dopamine interaction or the dopamine-glutamate interaction. It is now accepted that drug action can involve plural targets and that polypharmacological interaction with multiple targets, to address disease in more subtle and effective ways, is a key concept for development of novel drug candidates against complex CNS diseases. A multi-target therapeutic strategy for Alzheimer's disease resulted in the development of very effective Multi-Target Designed Ligands (MTDL) that act on both the cholinergic and monoaminergic systems, and also retard the progression of neurodegeneration by inhibiting amyloid aggregation. Many compounds already in databases have been investigated as ligands for multiple targets in drug discovery programs. A probabilistic method, the ParzenRosenblatt Window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. Based on all these findings, it is concluded that multipotent ligands targeting AChE/MAO-A/MAO-B and also D-1-R/D-2-R/5-HT2A-R/H-3-R are promising novel drug candidates with improved efficacy and beneficial neuroleptic and procognitive activities in treatment of Alzheimer's and related neurodegenerative diseases. Structural information for drug targets permits docking and virtual screening and exploration of the molecular determinants of binding, hence facilitating the design of multi-targeted drugs. The crystal structures and models of enzymes of the monoaminergic and cholinergic systems have been used to investigate the structural origins of target selectivity and to identify molecular determinants, in order to design MTDLs.
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.
Drying process in vapor swollen heterogels
(Springer, 2010) Erdogan, Matem; Pekcan, Önder
Disk-shaped heterogels were prepared by combining methyl methacrylate (MMA) and styrene (S) with ethylene glycol dimethacrylate (EGDM) as a crosslinker agent in the presence of 22'-azobisisobutyronitrile (AIBN). Swelling experiments were performed under chloroform vapor and the swollen gels are then allowed to dry under room temperature. Gravimetric technique was used to study drying processes. It is observed that two different regimes are present in the drying processes of these heterogels. Fickian diffusion model was used to determine desorption coefficients for each drying step in both regimes. Desorption coefficients D (d) of heterogels were found to be strongly correlated with the mixture composition of polymeric materials in the heterogel system for both regimes. Heterogels with high S content dry much slower than the heterogels with low S content.
Citation - WoS: 5
Citation - Scopus: 6
Effect of Lcst on the Swelling of Paam-Nipa Copolymers: a Fluorescence Study
(Springer, 2012) Evingür, Gülşen Akin; Pekcan, Önder
Temperature sensitive copolymers were prepared by free radical crosslinking copolymerization in aqueous solution with different molar percentage of N-isopropylacrylamide (NIPA) and acrylamide (AAm) monomers. NN'-methylenebis (acrylamide) (BIS) and ammonium persulfate (APS) were used as a crosslinker and an initiator respectively. The steady-state fluorescence (SSF) technique was used to determine the low critical phase transition temperature (LCST) for PAAm-NIPA copolymers. Swelling experiments were performed in water at various temperatures by real time monitoring of pyranine (Py) fluorescence intensity I which decreased as swelling proceeded. The Stern-Volmer equation is modified for low quenching efficiencies to interpret the behavior of pyranine intensity during the swelling of PAAm-NIPA copolymers. The Li-Tanaka equation was used to determine the swelling time constants tau (1) and the cooperative diffusion coefficients D (0) from fluorescence intensity weight and volume variations of the copolymers at various temperatures. It was observed that tau (1) first increased up to LCST and then decreased
Citation - WoS: 3
Citation - Scopus: 4
The Effects of Dea:water Ratio on the Properties of Zno Nanofilms Obtained by Spin Coating Method
(Elsevier Science, 2014) Akkaya Arier, Ümit Özlem; Uysal, Bengü Özuğur
In this work the ZnO were fabricated with the sol-gel spin coating method and the effects of the Dea:water ratios on the properties of the as-prepared ZnO thin films were determined by using a X-ray diffractometer transmission electron microscope scanning electron microscope atomic force microscope ultraviolet-visible spectrophotometer and spectrophotometer. Experimental results indicated that the Dea:water ratio affected the structural and optical properties of the ZnO films considerably. The activation energy for the particle growth of ZnO nanofilms and the effects of the Dea:water ratios on the band gap values of the ZnO films were investigated. The film has an activation energy of 26.3 kJ/mol and optical band gap of 3.27-3.31 eV is proportional to the Dea:water ratio. (c) 2014 Elsevier Ltd. All rights reserved.
Citation - WoS: 40
Citation - Scopus: 41
Effects of Gnp Addition on Optical Properties and Band Gap Energies of Pmma Films
(Wiley, 2019) Mergen, Ömer Bahadır; Arda, Ertan; Kara, Selim; Pekcan, Önder
In this study the effects of graphene nanoplatelet (GNP) doping on the optical parameters (absorption coefficient alpha and extinction coefficient k) and the optical transition energies (optical band gap and Urbach energies) of poly(methyl methacrylate)/graphene nanoplatelet (PMMA/GNP) composite films were studied. PMMA/GNP composite films with various GNP mass fractions were prepared by spin coating technique. The absorbance (A) changes of the prepared composites were measured by using UV-Vis technique. The alpha and k values of the composites were obtained from UV-Vis data. The observed rapid increase in A values in UV-region were associated with the optical transitions of GNP electrons from valence to conduction band. The direct (E-d) and indirect (E-i) optical band gap energies of the composites were determined by using Tauc method. Both of the band gap energies were decreased when the GNP content in the PMMA matrix is increased. The decrease in the band gap energies was interpreted as evidence of increased conductivity of the composites. Additionally energies of the band tails (Urbach energy) were calculated. It was seen that the Urbach energy levels were increased with GNP content. POLYM. COMPOS. 40:1862-1869 2019. (c) 2018 Society of Plastics Engineers
Citation - WoS: 1
Energy Needs for Drying of Paam- Kappa C Composites Prepared With Various Kappa C Contents
(European Polymer Federation, 2011) Pekcan, Önder; Evingür, Gülşen Akın
Various polyacrylamide (PAAm) - Kappa Carrageenan (kappa C) composite gels were prepared from acrylamide (AAm) N N'- methylenebisacrylamide (BIS) and different kappa C contents by free radical crosslinking copolymerization in water. Pyranine (P) was introduced as a fluorescence probe and scattered light I-sc and fluorescence intensities I from these gels were monitored during drying at different temperature. The fluorescence intensity of pyranine increased as drying time is increased for all samples. The behavior of I was quantified using the Stern-Volmer equation with moving boundary diffusion model. Desorption coefficient D increased as temperature was increased for a given kappa C content. Supporting gravimetrical and volumetric experiments were also carried out during drying of PAAm-kappa C composite gels. The energy Delta E values were measured for the drying processes for each kappa C content gel by using fluorescence gravimetrical and volumetric methods respectively. It is understood that Delta E values increase by increasing kappa C content indicating that energy needs for the drying of high kappa C content gel is larger than low kappa C content gel.

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