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Ozpolat, B.

Publications and source records attributed to Ozpolat, B..

2 recordsLinked to original sources

Predicting Future SARS-CoV-2 Mutations using Deep Learning

SARS-CoV-2 continues to spread over the world steadily as opposed to many earlier estimations that it would disappear in less than two years. Even though SARS-CoV-2 vaccines have reduced the speed of the infection significantly, they could not fully stop it. On the contrary, the World Health Organization has recently published cautionary statements that infection counts are on the rise, and a huge wave is expected in winter. Vaccines mostly target specific regions of the virus. The high mutation rate of SARS-CoV-2 is one essential tool that the virus exploits to escape from the available vaccines. Therefore, researchers have been working on designing next-generation vaccines against the new variants of the virus. Nevertheless, SARS-CoV-2 acquires new mutations faster than we can adapt our vaccines due to long clinical trial periods. Hence, there is a need for computational tools that can predict future SARS-CoV-2 mutations before they even emerge. In this paper, we propose several deep-learning-based methods to estimate the possible future mutations in SARS-CoV-2 genome. We design and evaluate various ensemble and bagging architectures enriched with a large set of genomic, biochemical, and phylogenetic features. We evaluate our models on the GISAID data and demonstrate that the best-performing methods achieve an F1-Macro score of 0.78.

bioinformatics↗

Target-driven design of a coumarinyl chalcone scaffold based novel EF2 Kinase inhibitor suppresses breast cancer growth in vivo

Eukaryotic elongation factor 2 kinase (eEF-2K), an unusual alpha kinase, is involved in protein synthesis through phosphorylation of elongation factor 2 (EF2). eEF-2K is indicated as one of the critical drivers of breast cancer and associated with poor clinical prognosis, representing a potential molecular target. The crystal structure of eEF-2K is unknown and there is no potent and effective eEF-2K inhibitor reported for clinical applications. To meet this challenge, we designed and synthesized several generations of potential inhibitor compounds and performed in silico studies. The effect of the inhibitors at the binding pocket of eEF-2K is analyzed after developing a 3D target model by homology modeling approaches using a domain of another -kinase called myosin heavy-chain kinase A (MHCKA) that is closely resembling eEF-2K. Our results showed that compounds with coumarin-chalcone cores have a high predicted binding affinity for binding to eEF-2K. Following in vitro studies, we identified a compound that was highly effective in inhibiting eEF-2K activity at submicromolar concentrations and inhibited proliferation of various breast cancer cells with different features (BT20, MDA-MB-231, MDA-MB-436 and MCF-7) by induction of apoptosis while sparing normal cells. In vivo systemic administration of the the lead inhibitor encapsulated in single lipid-based nanoparticles twice a week significantly supressed growth of MDA-MB-231 tumors in orthotopic breast cancer models in nude mice. In conclusion, our study provides the first in vivo effective small molecule eEF-2K inhibitor that may be used for molecularly targeted precison medicine strategies in breast cancer or other eEF-2K-dependent tumors.

cancer biology↗