Akdoğan, Ebru Demet
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Akdoğan, E.
Akdoğan, EBRU DEMET
E. D. Akdoğan
A., Ebru Demet
Ebru Demet Akdoğan
Akten E.
Akdoğan,E.D.
AKDOĞAN, EBRU DEMET
Akdogan,Ebru Demet
Akdogan,E.D.
Akdogan, Ebru Demet
Ebru Demet AKDOĞAN
E. Akdoğan
EBRU DEMET AKDOĞAN
Ebru Demet, Akdogan
Akdoğan, Ebru Demet
Akdoğan, E. D.
A.,Ebru Demet
AKDOĞAN, Ebru Demet
Demet Akdoğan, Ebru
Akten, Ebru Demet
Akdoğan, Ebru Demet
Akdoğan, Ebru Demet
Akdoğan, Demet Akten
Akdoğan, EBRU DEMET
E. D. Akdoğan
A., Ebru Demet
Ebru Demet Akdoğan
Akten E.
Akdoğan,E.D.
AKDOĞAN, EBRU DEMET
Akdogan,Ebru Demet
Akdogan,E.D.
Akdogan, Ebru Demet
Ebru Demet AKDOĞAN
E. Akdoğan
EBRU DEMET AKDOĞAN
Ebru Demet, Akdogan
Akdoğan, Ebru Demet
Akdoğan, E. D.
A.,Ebru Demet
AKDOĞAN, Ebru Demet
Demet Akdoğan, Ebru
Akten, Ebru Demet
Akdoğan, Ebru Demet
Akdoğan, Ebru Demet
Akdoğan, Demet Akten
Job Title
Prof. Dr.
Email Address
Main Affiliation
Molecular Biology and Genetics
Status
Current Staff
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ORCID ID
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Sustainable Development Goals
11
SUSTAINABLE CITIES AND COMMUNITIES
0
Research Products
17
PARTNERSHIPS FOR THE GOALS
0
Research Products
14
LIFE BELOW WATER
0
Research Products
8
DECENT WORK AND ECONOMIC GROWTH
0
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15
LIFE ON LAND
0
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1
NO POVERTY
0
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7
AFFORDABLE AND CLEAN ENERGY
0
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6
CLEAN WATER AND SANITATION
0
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12
RESPONSIBLE CONSUMPTION AND PRODUCTION
0
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16
PEACE, JUSTICE AND STRONG INSTITUTIONS
0
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9
INDUSTRY, INNOVATION AND INFRASTRUCTURE
0
Research Products
3
GOOD HEALTH AND WELL-BEING
2
Research Products
2
ZERO HUNGER
0
Research Products
4
QUALITY EDUCATION
0
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10
REDUCED INEQUALITIES
0
Research Products
13
CLIMATE ACTION
0
Research Products
5
GENDER EQUALITY
0
Research Products
Documents
23
Citations
217
h-index
8
Documents
37
Citations
658
Scholarly Output
39
Articles
27
Views / Downloads
245/15367
Supervised MSc Theses
8
Supervised PhD Theses
0
WoS Citation Count
238
Scopus Citation Count
250
WoS h-index
9
Scopus h-index
9
Patents
0
Projects
0
WoS Citations per Publication
6.10
Scopus Citations per Publication
6.41
Open Access Source
27
Supervised Theses
8
| Journal | Count |
|---|---|
| Journal of Biomolecular Structure and Dynamics | 3 |
| Journal of Computer-Aided Molecular Design | 2 |
| Archives of Biochemistry and Biophysics | 2 |
| Molecular Informatics | 2 |
| Biophysical Journal | 1 |
Current Page: 1 / 5
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39 results
Scholarly Output Search Results
Now showing 1 - 10 of 39
Conference Object Investigation of Allosteric Communication Pathways in Human Beta 2-Adrenergic Receptor(Wiley-Blackwell, 2015) Akdaş, Başak; Kürkçüoğlu, Özge; Doruker, Pemra; Akten, Ebru Demet[Abstract Not Available]Article Citation - WoS: 1Citation - Scopus: 1Tunnel-Like Region Observed as a Potential Allosteric Site In Staphylococcus Aureus Glyceraldehyde-3 Dehydrogenase(Elsevier Science inc, 2024) Guner-Yilmaz, Ozde Zeynep; Kurkcuoglu, Ozge; Akten, Ebru DemetGlyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzing the sixth step of glycolysis has been investigated for allosteric features that might be used as potential target for specific inhibition of Staphylococcus aureus (S.aureus). X-ray structure of bacterial enzyme for which a tunnel-like opening passing through the center previously proposed as an allosteric site has been subjected to six independent 500 ns long Molecular Dynamics simulations. Harmonic bond restraints were employed at key residues to underline the allosteric feature of this region. A noticeable reduction was observed in the mobility of NAD+ binding domains when restrictions were applied. Also, a substantial decrease in cross-correlations between distant C alpha fluctuations was detected throughout the structure. Mutual information (MI) analysis revealed a similar decrease in the degree of correspondence in positional fluctuations in all directions everywhere in the receptor. MI between backbone and sidechain torsional variations changed its distribution profile and decreased considerably around the catalytic sites when restraints were employed. Principal component analysis clearly showed that the restrained state sampled a narrower range of conformations than apo state, especially in the first principal mode due to restriction in the conformational flexibility of NAD+ binding domain. Clustering the trajectory based on catalytic site residues displayed a smaller repertoire of conformations for restrained state compared to apo. Representative snapshots subjected to k-shortest pathway analysis revealed the impact of bond restraints on the allosteric communication which displayed distinct optimal and suboptimal pathways for two states, where observed frequencies of critical residues Gln51 and Val283 at the proposed site changed considerably.Master Thesis Pharmacophore- Based Screening and Docking for the Discovery of Novel Antagonists of Beta-2 Adrenergic Receptor(Kadir Has Üniversitesi, 2013) Yakar, Rüya; Akdoğan, Ebru Demetß2AR which is the member of rhodopsin-like GPCR is the target system for the discovery of novel antagonists using structure-based pharmacophore modeling and docking methods. initially a shared pharmacophore model is obtained using the structure of five known inactive ß2AR complex (PDB ids: 2HR1 3D4S 3NY8 3NY9 and 3NYA). in order to test the discriminatory power of pharmacophore model a small database consisting of 117 known molecules (53 antagonists against 64 agonists) was screened using LigandScout software tool. The screening yielded 44 antagonists (72% true positives) against 17 agonists (18% false positives) which was found satisfactory. Then under the same screening conditions the second database that is the clean drug-like subset of ZiNC database was screened. -- Abstract'tan.Article Citation - WoS: 3Citation - Scopus: 3Transmembrane Helix 6 Observed at the Interface of Beta(2)ar Homodimers in Blind Docking Studies(Taylor & Francis Inc, 2015) Koroğlu, Ayça; Akten, Ebru DemetPeptide- 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 preferred to be near TM5 and TM6 regions of the receptor. Furthermore longer peptides generated from a whole TM region were blindly docked to beta(2)AR using the same rigid body approach. This yielded a total of seven docked peptides each derived from one TM helix. Most interestingly for each peptide TM6 was among the most preferred binding site region in the receptor. Besides the peptide dockings two beta(2)AR monomers were blindly docked to each other using a full rigid-body search of docking orientations which yielded a total of 16000 dimer conformations. Each dimer was then filtered according to a fitness value based on the membrane topology. Among 149 complexes that met the topology requirements 102 conformers were composed of two monomers oriented in opposite directions whereas in the remaining 47 the monomers were arranged in parallel. Lastly all 149 conformers were clustered based on a root mean-squared distance value of 6 angstrom. In agreement with the peptide results the clustering yielded the largest population of conformers with the highest Z-score value having TM6 at the interface region.Article Classification of Distinct Conformers of Beta < 2-Adrenergic Receptor (beta 2-Ar) Based on Binding Affinity of Ligands Through Docking Studies(Amer Chemical Soc, 2016) Akten, Ebru Demet; Dilcan, GoncaB2AR 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 elde edilmiştir. Snapshotlar derlenerek bağlanma bölgesindeki beş anahtar rezidünün RMSD değerlerine göre gruplandırılmıştır. Toplamda 13 farklı konformasyon elde edilmiş ve 5 agonist, 4 ters agonist ve 4 antagonist molekülü her bir konformasyona ayrı ayrı ve 7 farklı skor fonksiyonu kullanılarak dock edilmiştir. En iyi yerleşen konformasyonlar bağlanma bölgesindeki anahtar rezidülerle olan yakınlığına göre seçilmiş ve hesaplanmıştır. Anahtar bölgeye yaklaşamayanlar elenmiş, kalanlar ise skor değerlerine göre sıralanmıştır. Bu sınıflandırma, kritik değerlendirme yapabilmek için MD konformasyonlarından önce aktivitesi bilinen aktif/inaktif kristal yapılara uygulanmıştır. Her skor fonksiyonu tarafından seçilen ve ilk 5'te bulunan MD konformasyonları aktif ve inaktif olarak sınıflandırılmıştır. Son olarak, MD konformasyonlarının ayırt ediciliğini analiz edebilmek için, seçilen bu konformasyonlar ile küçük bir dataset kullanılarak sanal tarama yapılmıştır. MD konformasyonlarının inaktif kristal yapıya göre antagonist/ters agonistler için daha seçici olduğu gözlemlenmiştir. Reseptörün alternatif konformasyonlarını üretmek ve onları sınıflandırmak, genellikle tek bir snaphot X-ray örneği ile sınırlandırılmış ilaç tasarımı çalışmalarında önemli rol oynamaktadır.Article Citation - WoS: 4Citation - Scopus: 4Altered Dynamics of S. Aureus Phosphofructokinase Via Bond Restraints at Two Distinct Allosteric Binding Sites(Academic Press Ltd- Elsevier Science Ltd, 2022) Celebi, Metehan; Akten, Ebru DemetThe effect of perturbation at the allosteric site was investigated through several replicas of molecular dynamics (MD) simulations conducted on bacterial phosphofructokinase (SaPFK). In our previous work, an alternative binding site was estimated to be allosteric in addition to the experimentally reported one. To highlight the effect of both allosteric sites on receptor's dynamics, MD runs were carried out on apo forms with and without perturbation. Perturbation was achieved via incorporating multiple bond restraints for residue pairs located at the allosteric site. Restraints applied to the predicted site caused one dimer to stiffen, whereas an increase in mobility was detected in the same dimer when the experimentally resolved site was restrained. Fluctuations in C-alpha-C-alpha distances which is used to disclose residues with high potential of communication indicated a marked increase in signal transmission within each dimer as the receptor switched to a restrained state. Cross-correlation of positional fluctuations indicated an overall decrease in the magnitude of both positive and negative correlations when restraints were employed on the predicted allosteric site whereas an exact opposite effect was observed for the reported site. Finally, mutual correspondence between positional fluctuations noticeably increased with restraints on predicted allosteric site, whereas an opposite effect was observed for restraints applied on experimentally reported one. In view of these findings, it is clear that the perturbation of either one of two allosteric sites effected the dynamics of the receptor with a distinct and contrasting character. (c) 2022 Elsevier Ltd. All rights reserved.Conference Object Docking-Based Virtual Screening for Potential Activity Against Bacterial Pyruvate Kinase(Springer, 2017) Ergün, Çağla; Akten, Ebru Demet; Doruker, Pemra[Abstract Not Available]Article Citation - WoS: 18Citation - Scopus: 18Investigation of Allosteric Coupling in Human Beta(2)-Adrenergic Receptor in the Presence of Intracellular Loop 3(BMC, 2016) Özgür, Canan; Doruker, Pemra; Akten, Ebru DemetBackground: 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 blocked its accessibility to G protein. Simultaneously an outward tilt of transmembrane helix 5 (TM5) caused an expansion of the extracellular ligand-binding site. In the current study we performed independent runs with a total duration of 4 mu s to further investigate the very inactive state with packed ICL3 and the allosteric coupling event (three unrestrained runs and five runs with bond restraints at the ligand-binding site). Results: In all three independent unrestrained runs (each 500 ns long) ICL3 preserved its initially packed/closed conformation within the studied time frame suggesting an inhibition of the receptor's activity. Specific bond restraints were later imposed between some key residues at the ligand-binding site which have been experimentally determined to interact with the ligand. Restraining the binding site region to an open state facilitated ICL3 closure whereas a relatively constrained/closed binding site hindered ICL3 packing. However the reverse operation i.e. opening of the packed ICL3 could not be realized by restraining the binding site region to a closed state. Thus any attempt failed to free the ICL3 from its locked state due to the presence of persistent hydrogen bonds. Conclusions: Overall our simulations indicated that starting with very inactive states the receptor stayed almost irreversibly inhibited which in turn decreased the overall mobility of the receptor. Bond restraints which represented the geometric restrictions caused by ligands of various sizes when bound at the ligand-binding site induced the expected conformational changes in TM5 TM6 and consequently ICL3. Still once ICL3 was packed the allosteric coupling became ineffective due to strong hydrogen bonds connecting ICL3 to the core of the receptor.Conference Object Effect of Intracellular Loop 3 on Intrinsic Dynamics of Human Β2-Adrenergic Receptor(Cell Press, 2014) Ozcan, Ozer; Uyar, Arzu; Doruker, Pemra; Akten, Ebru Demet[No Abstract Available]Master Thesis Exploring Distinct Conformers of B2-Adrenergic Receptor Via Coarse-Grained Molecular Dynamics Simulations(Kadir Has Üniversitesi, 2012) Çakan, Sibel; Akdoğan, Demet Aktenß2AR, G protein bağlantılı reseptör ve birçok ilaç için hedef moleküldür. Reseptörünson derece esnek olan yapısı bir çok ligant molekülünü tanıma özelliği sağlar. Sonyıllarda yapılan kristalografik çalışmalar reseptörün aktif ve inaktif yapısını ortayaçıkarmasına rağmen bu çalışmalar reseptörün tüm dinamiğini çözmek için yeterlideğildir. Moleküler dinamik (MD) metodu reseptörün tüm dinamiğini anlamak içinalternatif ve verimli bir yöntemdir. Ancak geleneksel atomistik simülasyonlar birçokbiyolojik olayın gerçekleştiği zaman aralığı olan milisaniye seviyelerine ulaşamaz.Bu nedenle, bu calışmada serbestlik derecesini azaltan kaba taneli modellemekullanıldı. Sistem POPC membran tabakası içine gömülü ß2AR ve sulardanoluşturuldu. CG model kullanılmasının asıl amacı atomistik modellerde mümkünolmayan daha geniş yapısal alanı ortaya çıkarmaktır. Reseptörün bölgesel hareketleriatomistik simülasyonlarla uyum içindedir. CG simülasyondan dört görüntü seçilmişve geri eşleme yöntemi ile atomistik modele çevrilmiştir. Daha sonra herbiri 100 nsuzunluğunda bir MD simülasyonuna tabi tutulmuştur. Enerjik ve yapısal olarak farklıreseptör yapıları ortaya çıkmıştır. CG MD simülasyonunun PCA analizi, ilk beşbirincil bileşenin tüm dinamiğin %50 sini açıklarken, atomistik simülasyonların %85ini açıkladığını göstermiştir. CG ve atomistik öz-vektörlerin maksimum örtüşmedeğeri 0.46 dır. CG modelde atomistik modele göre korelasyonlar daha zayıftır.
