Browsing by Author "Akten, Ebru Demet"
Now showing items 1-19 of 19
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A Docking Study Using Atomistic Conformers Generated via Elastic Network Model for Cyclosporin A/Cyclophilin A Complex
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Publisher and Date:(Taylor & Francis Inc, 2009)Anisotropic network model is used to generate a set of distinct conformations for cylophilin A (CypA). The native structure is deformed to different extents along each of the lowest-frequency modes (first 7 modes) both in negative and positive directions. Each node of the elastic network represents either a single atom in the high-resolution model or a single residue in the low-resolution model. Realistic conformations with energies close to or lower than the crystal structure and with satisfactory ...
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Assessing protein-ligand binding modes with computational tools: the case of PDE4B
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Publisher and Date:(Springer, 2017)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 ...
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Blind Dockings of Benzothiazoles to Multiple Receptor Conformations of Triosephosphate Isomerase from Trypanosoma cruzi and Human
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Publisher and Date:(Wiley-VCH Verlag GmbH, 2011)We aim to uncover the binding modes of benzothiazoles which have been reported as specific inhibitors of triosephosphate isomerase from the parasite Trypanosoma cruzi (TcTIM) by performing blind dockings on both TcTIM and human TIM (hTIM). Detailed analysis of binding sites and specific interactions are carried out based on ensemble dockings to multiple receptor conformers obtained from molecular dynamics simulations. In TcTIM dimer dockings the inhibitors preferentially bind to the tunnel-shaped ...
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Classification Of Distinct Conformers Of Beta < 2-Adrenergic Receptor (Beta 2-AR) Based On Binding Affinity Of Ligands Through Docking Studies
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Publisher and Date:(Amer Chemical Soc, 2016)B2AR reseptörü, akciğerlerin rahatlamasında ve kardiyovasküler fizyolojide rol oynamasıyla önemli bir ilaç hedefidir. Bu çalışmada, çeşitli B2AR konformasyonlarını aktif veya inaktif olarak sınıflandırmak amacıyla, aktivitesi bilinen ligantlar seçilerek onların bağlanma şekillerine göre bir sınıflandırma stratejisi oluşturulmuştur. Önceki bir çalışmada gerçekleştirilen, reseptörün inaktif halinin 2.8 μs'lik MD simülasyonunda, ligandın bağlanma bölgesinin farklı konformasyonları ...
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Classification of distinct conformers of beta-2 adrenergic receptor based on binding affinity of ligands through docking studies
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Publisher and Date:(Kadir Has University, 2017)?2AR is an important drug target and plays a critical role in the relaxation of pulmonary tissues and cardiovascular physiology. We have developed a strategy for classifying various ?2AR conformers as active or inactive states based on binding mode of selected ligands with known activities. Previously distinct conformational states of the ligand’s binding pocket were obtained from a 2.8 µs MD simulation. Snapshots were clustered based on RMSD value of five key residues at the binding site. Clustering ...
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Discovery of high affinity ligands for beta(2)-adrenergic receptor through pharmacophore-based high-throughput virtual screening and docking
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Publisher and Date:(Elsevier Science Inc, 2014)Novel high affinity compounds for human beta(2)-adrenergic receptor (beta(2)-AR) were searched among the clean drug-like subset of ZINC database consisting of 9928465 molecules that satisfy the Lipinski's rule of five. The screening protocol consisted of a high-throughput pharmacophore screening followed by an extensive amount of docking and rescoring. The pharmacophore model was composed of key features shared by all five inactive states of beta(2)-AR in complex with inverse agonists and antagonists. ...
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Distinctive communication networks in inactive states of beta(2)-adrenergic receptor: Mutual information and entropy transfer analysis
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Publisher and Date:(Wiley, 2020)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 ...
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Docking-based virtual screening for potential activity against bacterial pyruvate kinase
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Publisher and Date:(Springer, 2017)
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Effect of Intracellular Loop 3 on Intrinsic Dynamics of Human beta 2-Adrenergic Receptor
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Publisher and Date:(Cell Press, 2014)
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Identification of Alternative Allosteric Sites in Glycolytic Enzymes for Potential Use as Species-Specific Drug Targets
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Publisher and Date:(Frontiers Media, 2020)Three allosteric glycolytic enzymes, phosphofructokinase, glyceraldehyde-3 phosphate dehydrogenase and pyruvate kinase, associated with bacterial, parasitic and human species, were explored to identify potential allosteric sites that would be used as prime targets for species-specific drug design purposes using a newly developed approach which incorporates solvent mapping, elastic network modeling, sequence and structural alignments. The majority of binding sites detected by solvent mapping ...
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Intrinsic Dynamics and Causality in Correlated Motions Unraveled in Two Distinct Inactive States of Human beta(2)-Adrenergic Receptor
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Publisher and Date:(Amer Chemical Soc, 2019)The alternative inactive state of the human beta(2)-adrenergic receptor originally exposed in molecular dynamics simulations was investigated using various analysis tools to evaluate causality between correlated residue-pair fluctuations and suggest allosteric communication pathways. A major conformational shift observed in the third intracellular loop (ICL3) displayed a novel inactive state featuring an inaccessible G protein binding site blocked by ICL3 and an expanded orthosteric ligand binding ...
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Investigation of allosteric communication pathways in human beta 2-adrenergic receptor
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Publisher and Date:(Wiley-Blackwell, 2015)
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Investigation of Allosteric Coupling in Human Beta(2)-Adrenergic Receptor in the Presence of Intracellular Loop 3
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Publisher and Date:(BMC, 2016)Background: This study investigates the allosteric coupling that exists between the intra- and extracellular parts of human beta(2)-adrenergic receptor (beta(2)-AR) in the presence of the intracellular loop 3 (ICL3) which is missing in all crystallographic experiments and most of the simulation studies reported so far. Our recent 1 mu s long MD run has revealed a transition to the so-called very inactive state of the receptor in which ICL3 packed under the G protein's binding cavity and completely ...
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Investigation of intrinsic dynamics and allosteric coupling in human beta 2-adrenergic receptor
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Publisher and Date:(Springer, 2017)
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Ligand-binding affinity of alternative conformers of human beta(2)-adrenergic receptor in the presence of intracellular loop 3 (ICL3) and their potential use in virtual screening studies
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Publisher and Date:(Wiley, 2019)This study investigates the structural distinctiveness of orthosteric ligand-binding sites of several human beta(2) adrenergic receptor (beta(2)-AR) conformations that have been obtained from a set of independent molecular dynamics (MD) simulations in the presence of intracellular loop 3 (ICL3). A docking protocol was established in order to classify each receptor conformation via its binding affinity to selected ligands with known efficacy. This work's main goal was to reveal many subtle features ...
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Molecular docking study based on pharmacophore modeling for novel PhosphodiesteraseIV ınhibitors
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Publisher and Date:(Wiley-VCH Verlag GmbH, 2012)In this study pharmacophore modelling was carried out for novel PhosphodiesteraseIV (PDEIV) inhibitors. A pharmacophore-based virtual screening which resulted in 1959 hit compounds was performed with six chemical databases. The pharmacophore screening was proven to be successful in discriminating active and inactive inhibitors using a set of compounds with known activity obtained from ChEMBL database. Furthermore the Lipinskis rule of five was applied for physicochemical filtering of the hit ...
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Poz- Adrenerjik Reseptörün Kaba Taneli Moleküler Dinamik Simülasyonu ile farklı Konformasyonlarının Araştırılması
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Publisher and Date:(Kadir Has University, 2012)ß2 adrenergic receptor (ß2AR) is a G protein-coupled receptor, which belongs to thelargest family of membrane proteins and is the target of many drugs. ß2AR is highlyflexible and, able to recognize a wide range of ligands through its conformationalvariations. Although recent crystallographic experiments have revealed active andinactive conformations, they are not sufficient for deciphering the whole receptor?sdynamics. Molecular dynamics (MD) simulation is an alternative and efficientmethod to ...
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Structural Analysis of Peptide Fragments Following The Hydrolysis of Bovine Serum Albumin by Trypsin and Chymotrypsin
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Publisher and Date:(Taylor & Francis Inc, 2016)Peptide bond hydrolysis of bovine serum albumin (BSA) by chymotrypsin and trypsin was investigated by employing time-resolved fluorescence spectroscopy. As a fluorescent cross-linking reagent N-(1-pyrenyl) maleimide (PM) was attached to BSA through all free amine groups of arginine lysine and/or single free thiol (Cys34). Time-resolved fluorescence spectroscopy was used to monitor fluorescence decays analyzed by exponential series method to obtain the changes in lifetime distributions. After the ...
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Transmembrane helix 6 observed at the interface of beta(2)AR homodimers in blind docking studies
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Publisher and Date:(Taylor & Francis Inc, 2015)Peptide- and protein-protein dockings were carried out on beta(2)-adrenergic receptor (beta(2)AR) to confirm the presence of transmembrane helix 6 (TM6) at the interface region between two beta(2)AR monomers thereby its possible role in dimerization as suggested in numerous experimental and computational studies. Initially a portion of TM6 was modeled as a peptide consisting of 23 residues and blindly docked to beta(2)AR monomer using a rigid body approach. Interestingly all highest score conformations ...
