Biyoinformatik ve Genetik Bölümü Koleksiyonu
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Article Citation Count: 2Aryl butenoic acid derivatives as a new class of histone deacetylase inhibitors: synthesis in vitro evaluation and molecular docking studies(Scientific Technical Research Council Turkey-Tubitak, 2014) Yelekçi, Kemal; Seven, özlem; Eymur, Guluzar; Tatar, Gamze Bora; Erden, Didem Dayangaç; Yelekçi, Kemal; Yurter, Hayat; Demir, Ayhan S.New aryl butenoic acid derivatives have been synthesized by combining hydroxy- or methoxy-substituted phenyl rings as the capping group with a double bond in the short linker as well as metal binding groups enoic ester and salts bearing either methyl or morpholine. These compounds have been shown to possess promising histone deacetylase inhibition activities via in vitro fluorometric assay and molecular docking studies.Conference Object Citation Count: 0Docking-based virtual screening for potential activity against bacterial pyruvate kinase(Springer, 2017) Ergün, Çağla; Akten, Ebru Demet; Doruker, Pemra[Abstract Not Available]Article Citation Count: 1Exploring distinct binding site regions of beta(2)-adrenergic receptor via coarse-grained molecular dynamics simulations(Scientific Technical Research Council Turkey-Tubitak, 2013) Akdoğan, Ebru Demet; Akdoğan, Ebru Demetbeta(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.Article Citation Count: 16In silico design of novel and highly selective lysine-specific histone demethylase inhibitors(Scientific Technical Research Council Turkey-Tubitak, 2011) Akdoğan, Ebru Demet; Yelekçi, Kemal; Yelekçi, KemalHistone 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.Conference Object Citation Count: 0Investigation of intrinsic dynamics and allosteric coupling in human beta 2-adrenergic receptor(Springer, 2017) Özcan, Özer; Özgür, Canan; Doruker, Pemra; Akten, Ebru Demet[Abstract Not Available]Article Citation Count: 6Novel Mutants of the Aubergine Gene(Taylor & Francis Inc, 2016) Şahin, H. Bahar; Karataş, Ömer Faruk; Specchia, Valeria; Di Tommaso, Silvia D.; Diebold, Celine; Bozzetti, Maria Pia; Giangrande, AngelaAubergine is an RNA-binding protein of the Piwi clade functioning in germline in the piRNA pathway that silences transposons and repetitive sequences. Several mutations of this gene exist but they mostly result in truncated proteins or correspond to mutations that also affect neighboring genes. We have generated complete aubergine knock-out mutants that do not disrupt the neighboring genes. These novel mutants are characterized by PCR and sequencing. Their nature is confirmed by female sterility and by the presence of crystals in testes common to the aubergine loss of function mutations. These mutants provide novel and more appropriate tools for the study of the piRNA pathway that controls genome stability.Article Citation Count: 5Power of inhibition activity screening and 3D molecular modeling approaches in HDAC 8 inhibitor design(Scientific Technical Research Council Turkey-Tubitak, 2011) Yelekçi, Kemal; Tokluman, Tenzile Deniz; Yelekçi, Kemal; Yurter, HayatIn-vitro inhibition activity screening and in-silico 3D molecular modeling approaches are important tools for design and development of specific histone deacetylase (HDAC) inhibitors. The objective of this study was to investigate the consistency between these 2 approaches. The HDAC 8 inhibition activities of 8 randomly selected different carboxylic acid derivatives were screened and in-vitro experimental results were compared with in-silico molecular modeling calculations. This study demonstrated that there is no sole gold standard technique for inhibitor design and it was concluded that a combination of molecular modeling and activity screening assays will ensure more comprehensive and dependable results.
