TR-Dizin İndeksli Yayınlar Koleksiyonu

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Browsing TR-Dizin İndeksli Yayınlar Koleksiyonu by Institution Author "Akdoğan, Ebru Demet"

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    Article
    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.
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    Article
    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.
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    Research Project
    Kompleks Proteinlerin Farklı Bölgelerindeki Amino Asit Dağılımı ve Etkileşimini Etkileyen Çevresel ve Yapısal Faktörlerin İncelenmesi: Hücre Zarı Ortamı, Sekonder Yapı ve Kompleks Yapıdaki Monomer Sayısı
    (2020) Akdoğan, Ebru Demet
    Bu projede kompleks yapılardaki amino asit türleri, dagılımları, görülme sıklıkları, çözücü ersilir yüzey alanı (SASA), arayüzeyde etkilesen amino asit çiftlerinin görülme sıklıkları ve kontakt derecelerini etkileyen yapısal ve çevresel faktörler ele alınarak, bu degisimler ayrıntılı bir sekilde ortaya konmustur. Bu faktörlerden biri olan kompleks yapının içinde bulundugu ortam ele alındıgında, hücre zarı proteinin hücre dısına tasan periferik ortamdaki arayüzey bölgesinin, hücre içi lipid ortamdaki arayüzey bölgesinden her yönden farklı oldugu gösterilmistir. Bir diger faktör de kompleks yapıyı olusturan monomerik birim sayısıdır. Alfasarmal kategorisinde yer alan dimerik, trimerik ve tetramerik yapılar amino asitlerin tür ve dagılımları, SASA, propansite ve arayüzey kontakt dereceleri, frekansları ve skor degerlerine göre karsılastırıldıgında her yönden dikkat çekici farklılıklar ortaya çıkmıstır. Son olarak sekonder yapıdaki degisikligin ne derece etkili bir faktör olacagını göstermek amacıyla, betasilindir yapılar kendi içlerinde incelenmis ve en büyük farklılık ta bu kategoride ortaya çıkmıstır. Bu bulgular dogrultusunda bir sonraki daha kapsamlı proje önerimizde gelistirilmesi planlanan arayüzey tahmin algoritması için kritik öneme sahip farklılıklar ortaya çıktıgından, her kategorinin kendi içinde ele alınması gerektigi ve faktörlerden en fazla hücre içi/dısı ortam ile sekonder yapının dikkate alınması gerektigi vurgulanmıstır