Gebze Technical UniversityKocaeli

Gebze, Turkey

Gebze Technical UniversityKocaeli

Gebze, Turkey
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Kocak A.,Gebze Technical UniversityKocaeli | Yildiz M.,Gebze Technical UniversityKocaeli
Journal of Molecular Graphics and Modelling | Year: 2017

The disruption of aspartoacylase enzyme's catalytic activity causes fatal neurodegenerative Canavan disease. By molecular dynamics and docking methods, here we studied two deleterious mutations that have been identified in the Canavan patients’ genotype E285A, F295S, and revealed the possible cause for the enzyme inhibition due to the drastic changes in active site dynamics, loss of interactions among Arg 71, Arg 168 and the substrate and pKa value of critical Glu178 residue. In addition to changes in the enzyme dynamics, free energy calculations show that the binding energy of substrate decreases dramatically up on mutations. © 2017 Elsevier Inc.

Keris-Sen U.D.,Gebze Technical UniversityKocaeli | Gurol M.D.,Gebze Technical UniversityKocaeli
Biomass and Bioenergy | Year: 2017

In this study, ozone was used as a pretreatment method to improve the yield in enzymatic saccharification of microalgal carbohydrates by increasing the disruption of microalgal cells. Different ozone doses (0.25–2.0 g O3 g−1 dry weight biomass (DWB)) were applied to the algal suspensions before the enzymatic hydrolysis process, which was performed at various enzyme concentrations, enzymatic hydrolysis times and biomass concentrations. The highest glucose yield obtained was 80.6% (w/w) of total carbohydrates under the conditions of 2.5 g L−1 biomass concentration and 4 h hydrolysis time for 0.5 g O3 g−1 DWB ozone dose and 1.2 mL−1 g−1 DWB enzyme concentration. In addition to ozone pretreatment, the same algal culture was subjected to acid, alkaline and ultrasonic pretreatments. It was observed that application of ozone increased the glucose yield much higher than the other three pretreatment methods, indicating its great potential in production of bioethanol from microalgae. © 2017 Elsevier Ltd

Erol I.,Bahcesehir University | Erol I.,Gebze Technical UniversityKocaeli | Aksoydan B.,Bahcesehir University | Kantarcioglu I.,Bahcesehir University | And 2 more authors.
Journal of Molecular Graphics and Modelling | Year: 2017

The serotonin (5-hydroxytryptamine, 5HT) transporter (SERT) is a member of neurotransmitter sodium symporter (NSS) family, which maintains neurotransmitter by reuptaking 5HT into synapses. Decrease in serotonin concentrations in synaptic clefts have been reported to cause psychological and neurological disorders. Therefore, inhibition of SERT is a potent strategy for the treatment of related diseases such as depression. In this study, approximately 260,000 small molecules from an available chemical database have been virtually screened both at central and allosteric binding sites of SERT to identify potent novel candidate SERT inhibitors. A set of docking algorithms were used to predict binding modes and energies of compounds. Screening analyses led three top-ranked hit compounds (160234, Otava ID: 7118020138; 159166, Otava ID: 7117171303; and 69419, Otava ID: 118671819) for central binding site (S1) and one compound (93507, Otava ID: 6248262) for allosteric binding site (S2). These promising compounds are then subjected to long multiple molecular dynamics (MD) simulations to elucidate their structural and dynamical profiles at the binding cavities of SERT. Higher predicted binding affinities of identified compounds were also confirmed with binding free energy calculations (MM/GBSA) in comparison with the reference central and allosteric binding site inhibitors, paroxetine (8PR) and escitalopram (68P), respectively. To the best of our knowledge, the present work is the first structure-based high throughput virtual screening study reported using recently revealed crystal structure of SERT for screening inhibitors from chemical databases on S1 and S2 binding sites. Small molecule library screening study yielded candidate compounds both at central and allosteric binding site of SERT, and further experimentation may pave the way for developing novel strong inhibitors. © 2017 Elsevier Inc.

Durdagi S.,Bahcesehir University | Erol I.,Bahcesehir University | Erol I.,Gebze Technical UniversityKocaeli | Salmas R.E.,Bahcesehir University | And 2 more authors.
Journal of Molecular Graphics and Modelling | Year: 2017

The intra-cavitary drug blockade of hERG1 channel has been extensively studied, both experimentally and theoretically. Structurally diverse ligands inadvertently block the hERG1 K+ channel currents lead to drug induced Long QT Syndrome (LQTS). Accordingly, designing either hERG1 channel openers or current activators, with the potential to target other binding pockets of the channel, has been introduced as a viable approach in modern anti-arrhythmia drug development. However, reports and investigations on the molecular mechanisms underlying activators binding to the hERG1 channel remain sparse and the overall molecular design principles are largely unknown. Most of the hERG1 activators were discovered during mandatory screening for hERG1 blockade. To fill this apparent deficit, the first universal pharmacophore model for hERG1 K+ channel activators was developed using PHASE. 3D structures of 18 hERG1 K+ channel activators and their corresponding measured binding affinity values were used in the development of pharmacophore models. These compounds spanned a range of structurally different chemotypes with moderate variation in binding affinity. A five sites AAHRR (A, hydrogen-bond accepting, H, hydrophobic, R, aromatic) pharmacophore model has shown reasonable high statistical results compared to the other developed more than 1000 hypotheses. This model was used to construct steric and electrostatic contour maps. The predictive power of the model was tested with 3 external test set compounds as true unknowns. Finally, the pharmacophore model was combined with the previously developed receptor-based model of hERG1 K+ channel to develop and screen novel activators. The results are quite striking and it suggests a greater future role for pharmacophore modeling and virtual drug screening simulations in deciphering complex patterns of molecular mechanisms of hERG1 channel openers at the target sites. The developed model is available upon request and it may serve as basis for the synthesis of novel therapeutic hERG1 activators. © 2017

Aydin M.,Gebze Technical UniversityKocaeli | Aydin M.,Namik Kemal University | Gorur M.,Istanbul Medeniyet University | Yilmaz F.,Gebze Technical UniversityKocaeli
Reactive and Functional Polymers | Year: 2016

A new hexa-armed star polymer bearing 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-pending polymer chains emanating from a phosphazene core (P2) was prepared and used as the cathode material in Li-ion battery assembly. The properties of the assembled battery (BP2) were compared with those of BL2 assembled using its linear counterpart (L2). Their spin concentrations investigated via solution electron spin resonance (ESR) measurements were found to be almost the same. The charge/discharge capacities and energy densities of BP2 were considerably higher than those of BL2. However, they exhibited comparable charge/discharge efficiencies and their discharge capacities dropped to similar percentages of their initial values. © 2016 Elsevier B.V. All rights reserved.

Chu M.,Grupo de Biotecnologia de Frutales | Quinonero C.,Grupo de Biotecnologia de Frutales | Akdemir H.,Gebze Technical UniversityKocaeli | Alburquerque N.,Grupo de Biotecnologia de Frutales | And 2 more authors.
Biotechnology Progress | Year: 2016

Although some works have explored the transformation of differentiated, embryogenic suspension-cultured cells (SCC) to produce transgenic grapevine plants, to our knowledge this is one of the first reports on the efficient transformation of dedifferentiated Vitis vinifera cv Monastrell SCC. This protocol has been developed using the sonication-assisted Agrobacterium-mediated transformation (SAAT) method. A construct harboring the selectable nptII and the eyfp/IV2 marker genes was used in the study and transformation efficiencies reached over 50 independent transformed SCC per gram of infected cells. Best results were obtained when cells were infected at the exponential phase. A high density plating (500 mg/dish) gave significantly better results. As selective agent, kanamycin was inefficient for the selection of Monastrell transformed SCC since wild type cells were almost insensitive to this antibiotic whereas application of paromomycin resulted in very effective selection. Selected eyfp-expressing microcalli were grown until enough tissue was available to scale up a new transgenic SCC. These transgenic SCC lines were evaluated molecularly and phenotypically demonstrating the presence and integration of both transgenes, the absence of Agrobacterium contamination and the ability of the transformed SCC to grow in highly selective liquid medium. The methodology described here opens the possibility of improving the production of valuable metabolites. © 2016 American Institute of Chemical Engineers.

Ertekin O.,Scientific and Technological Research Council of Turkey | Ertekin O.,Gebze Technical UniversityKocaeli | Ozturk S.,Scientific and Technological Research Council of Turkey | Ozturk Z.Z.,Gebze Technical UniversityKocaeli
Sensors (Switzerland) | Year: 2016

This study introduces the use of an IgA isotype aflatoxin (AF) specific monoclonal antibody for the development of a highly sensitive Quartz Crystal Microbalance (QCM) immunobiosensor for the detection of AF in inhibitory immunoassay format. The higher molecular weight of IgA antibodies proved an advantage over commonly used IgG antibodies in label free immunobiosensor measurements. IgA and IgG antibodies with similar affinity for AF were used in the comparative studies. Sensor surface was prepared by covalent immobilization of AFB1, using self assembled monolayer (SAM) formed on gold coated Quartz Crystal, with 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxy succinimide (EDC/NHS) method using a diamine linker. Nonspecific binding to the surface was decreased by minimizing the duration of EDC/NHS activation. Sensor surface was chemically blocked after AF immobilization without any need for protein blocking. This protein free sensor chip endured harsh solutions with strong ionic detergent at high pH, which is required for the regeneration of the high affinity antibody-antigen interaction. According to the obtained results, the detection range with IgA antibodies was higher than IgG antibodies in QCM immunosensor developed for AFB1. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

Aksakal F.,Gebze Technical UniversityKocaeli | Shvets N.,Gebze Technical UniversityKocaeli | Dimoglo A.,Kocaeli University
Journal of Molecular Graphics and Modelling | Year: 2015

Abstract Structural and electronic factors influencing selective inhibition of cyclooxygenase-2 and 5-lipoxygenase (COX-2/5-LOX) were studied by using Electronic-Topological Method combined with Neural Networks (ETM-NN), molecular docking, and Density Functional Theory (DFT) in a large set of molecules. The results of the ETM-NN calculations allowed for the selection of pharmacophoric molecular fragments, which could be taken as a basis for a system capable of predicting the COX-2/5-LOX inhibitory activity. For the more effective extraction of the pharmacophoric molecular fragments, docking of molecules into the active sites of the two enzymes was carried out to get data on the ligand-receptor interaction. To make an assessment of these interactions, stabilization energies were calculated by using Natural Bond Orbital (NBO) analysis. Docking and data on the electronic structures of active sites of enzymes helped to reveal effectively the peculiarities of the ligand-receptor binding. The system for the selective COX-2/5-LOX inhibitory activity prediction that has been developed as the result of the ETM-NN study recognized correctly 93% of compounds as highly active ones. Thus, this system can be successfully used for carrying out computer screening and synthesis of potent inhibitors of COX-2/5-LOX with diverse molecular skeletons. © 2015 Elsevier Inc.

Bulut A.,Bogazici University | Zorlu Y.,Gebze Technical UniversityKocaeli | Topkaya R.,Gebze Technical UniversityKocaeli | Aktas B.,Gebze Technical UniversityKocaeli | And 3 more authors.
Dalton Transactions | Year: 2015

Engineering a copper coordination sphere with organoimine ligands and tuning the organophosphonate protonation states produced [{Cu(2,2′-bpy)}2(HO3P(CH2)8PO3H2)4] (1) and [{Cu(terpy)}2(2,7-FDA-H2)2]·(2,7-FDA-H4)(2H2O) (2) (2,7-FDA-H4 = 2,7-fluorenonediphosphonic acid) macrocyclic copper-organophosphonate building blocks. 1 exhibits high temperature magnetic ordering, while 2 is paramagnetic. The structures were characterized by single crystal X-ray diffraction. This journal is © The Royal Society of Chemistry.

Inan H.,Gebze Technical UniversityKocaeli | Turkay O.,Gebze Technical UniversityKocaeli | Akkiris C.,Gebze Technical UniversityKocaeli
Desalination and Water Treatment | Year: 2016

This study aimed to investigate the effect of microwave (MW) and microwave–chemical (MWC) pretreatment on barley straw and to identify the acidic, basic, or oxidative chemicals that provide the highest sugar conversion for subsequent enzymatic hydrolysis. The MW and MWC processes were applied as a pretreatment step before fermentation. MW radiation at 200 and 300 W and MW radiation plus a chemical (H2SO4 or NaOH or H2O2) as catalyst were applied, and total sugar, total phenol, and Klason and acid-soluble lignin were measured. Although the MWC pretreatment produced a higher total sugar concentration than the MW pretreatment, the addition of an NaOH solution produced the best results in terms of all parameters. Fourier transform infrared analysis was also performed to observe the deterioration of molecular structures after the application of MW and MWC. © 2015 Balaban Desalination Publications. All rights reserved.

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