TR-Dizin İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://gcris.khas.edu.tr/handle/20.500.12469/4467

Browse

Now showing 1 - 4 of 4

Citation Count: 3
The effect of weekend curfews on epidemics: a Monte Carlo simulation
(Tubitak Scientific & Technical Research Council Turkey, 2021) Kaygusuz, Hakan; Berker, A. Nihat
The ongoing COVID-19 pandemic is being responded with various methods, applying vaccines, experimental treatment options, total lockdowns or partial curfews. Weekend curfews are among the methods for reducing the number of infected persons, and this method is practically applied in some countries such as Turkey. In this study, the effect of weekend curfews on reducing the spread of a contagious disease, such as COVID-19, is modeled using a Monte Carlo algorithm with a hybrid lattice model. In the simulation setup, a fictional country with three towns and 26,610 citizens were used as a model. Results indicate that applying a weekend curfew reduces the ratio of ill cases from 0.23 to 0.15. The results also show that applying personal precautions such as social distancing is important for reducing the number of cases and deaths. If the probability of disease spread can be reduced to 0.1, in that case, the death ratio can be minimized down to 0.
Citation Count: 14
Exploration of the binding pocket of histone deacetylases: the design of potent and isoform-selective inhibitors
(Tübitak, 2017) Yelekçi, Kemal; Yelekçi, Kemal
Histone deacetylases (HDACs) are enzymes that act on histone proteins to remove the acetyl group and thereby regulate the chromatin state. HDACs act not only on histone protein but also nonhistone proteins that are key players in cellular processes such as the cell cycle, signal transduction, apoptosis, and more. “Classical” HDACs have been shown to be promising targets for anticancer drug design and development. However, the selectivity of HDAC inhibitors for HDAC isoforms remains the motivation of current research in this field. Here, we explored Class I HDACs and HDAC6 by sequence alignment and structural superimposition, catalytic channel extraction, and identification of critical residues involved in HDAC catalysis. Based on the general pharmacophore features of known HDAC inhibitors, we developed a library of compounds by scaffold hopping on a fragment hit identified via structurebased virtual screening of the molecular fragment library retrieved from the Otava database. Molecular docking assay revealed five of these compounds to have increased potency and selectivity for HDACs 1 and 2. Furthermore, their predicted absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties were consistent with those of drug-like compounds. With further modelingbased and experimental investigations, we believe that these findings may offer additional potential HDAC inhibitors with improved selectivity
Citation Count: 0
Modelling of C-terminal tail of human STING and its interaction with tank-binding kinase 1
(Tubitak Scientific & Technical Research Council Turkey, 2022) Eşsiz, Şebnem; Audu-Bida, Hajara; Essiz, Sebnem
Stimulator of interferon genes (STING) plays a significant role in a cell's intracellular defense against pathogens or self DNA by inducing inflammation or apoptosis through a pathway known as cGAS-cGAMP-STING. STING uses one of its domains, the C-terminal tail (CTT) to recruit the members of the pathway. However, the structure of this domain has not been solved experimentally. STING conformation is open and more flexible when inactive. When STING gets activated by cGAMP, its conformation changes to a closed state covered by 4 beta-sheets over the binding site. This conformational change leads to its binding to Tank-binding kinase 1 (TBK1). TBK1 then phosphorylates STING aiding its entry to the cell's nucleus. In this study, we focused on the loop modeling of the CTT domain in both the active and inactive STING conformations. After the modeling step, the active and inactive STING structures were docked to one of the cGAS-cGAMP-STING pathway members, TBK1, to observe the differences of binding modes. CTT loop stayed higher in the active structure, while all the best-scored models, active or inactive, ended up around the same position with respect to TBK1. However, when the STING poses are compared with the cryo-EM image of the complex structure, the models in the active structure chain B displayed closer results to the complex structure.
Citation Count: 0
Modelling of C-terminal tail of human STING and its interaction with\rtank-binding kinase 1
(2022) Eşsiz, Şebnem; Bıda, Hajara Audu; Eşsiz, Şebnem
Stimulator of interferon genes (STING) plays a significant role in a cell’s intracellular defense against pathogens or selfDNA by inducing inflammation or apoptosis through a pathway known as cGAS-cGAMP-STING. STING uses one of its domains, the\rC-terminal tail (CTT) to recruit the members of the pathway. However, the structure of this domain has not been solved experimentally.\rSTING conformation is open and more flexible when inactive. When STING gets activated by cGAMP, its conformation changes to a\rclosed state covered by 4 beta-sheets over the binding site. This conformational change leads to its binding to Tank-binding kinase 1\r(TBK1). TBK1 then phosphorylates STING aiding its entry to the cell’s nucleus.\rIn this study, we focused on the loop modeling of the CTT domain in both the active and inactive STING conformations. After the\rmodeling step, the active and inactive STING structures were docked to one of the cGAS-cGAMP-STING pathway members, TBK1,\rto observe the differences of binding modes. CTT loop stayed higher in the active structure, while all the best-scored models, active or\rinactive, ended up around the same position with respect to TBK1. However, when the STING poses are compared with the cryo-EM\rimage of the complex structure, the models in the active structure chain B displayed closer results to the complex structure.

Browse

Browsing TR-Dizin İndeksli Yayınlar Koleksiyonu by WoS Q "Q3"