Structure prediction of eukaryotic elongation factor-2 kinase and identification of the binding mechanisms of its inhibitors: homology modeling, molecular docking, and molecular dynamics simulation

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dc.authoridTASKIN-TOK, Tugba/0000-0002-0064-8400
dc.authoridTatar Yilmaz, Gizem/0000-0001-6642-6870
dc.authoridOzpolat, Bulent/0000-0001-8602-7463
dc.contributor.authorTatar, Gizem
dc.contributor.authorTok, Tugba Taskin
dc.contributor.authorOzpolat, Bulent
dc.contributor.authorMehmet, A. Y.
dc.date.accessioned2025-01-27T20:11:42Z
dc.date.available2025-01-27T20:11:42Z
dc.date.issued2022
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractProtein kinases emerged as one of the most successful families of drug targets due to their increased activity and involvement in mediating critical signal transduction pathways in cancer cells. Recent evidence suggests that eukaryotic elongation factor 2 kinase (eEF-2K) is a potential therapeutic target for treating some highly aggressive solid cancers, including lung, pancreatic and triple-negative breast cancers. Thus, several compounds have been developed for the inhibition of the enzyme activity, but they are not sufficiently specific and potent. Besides, the crystal structure of this kinase remains unknown. Hence, the functional organization and regulation of eEF-2K remain poorly characterized. For this purpose, we constructed a homology model of eEF-2K and then used docking methodology to better understanding the binding mechanism of eEF-2K with 58 compounds that have been proposed as existing inhibitors. The results of this analysis were compared with the experimental results and the compounds effective against eEF-2K were determined against eEF-2K as a result of both studies. And finally, molecular dynamics (MD) simulations were performed for the stability of eEF-2K with these compounds. According to these study defined that the binding mechanism of eEF-2K with inhibitors at the molecular level and elucidated the residues of eEF-2K that play an important role in enzyme selectivity and ligand affinity. This information may lead to new selective and potential drug molecules to be for inhibition of eEF-2K.
dc.description.sponsorshipScientific and Technological Research Council of Turkey TUBITAK [215S008]
dc.description.sponsorshipThis work was financially supported by The Scientific and Technological Research Council of Turkey TUBITAK (project no: 215S008).
dc.identifier.doi10.1080/07391102.2019.1592024
dc.identifier.endpage13365
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.issue24
dc.identifier.pmid30880628
dc.identifier.scopus2-s2.0-85126435295
dc.identifier.scopusqualityQ1
dc.identifier.startpage13355
dc.identifier.urihttps://doi.org/10.1080/07391102.2019.1592024
dc.identifier.urihttps://hdl.handle.net/20.500.12428/20677
dc.identifier.volume40
dc.identifier.wosWOS:000767657600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Inc
dc.relation.ispartofJournal of Biomolecular Structure & Dynamics
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20250125
dc.subjectProtein kinases
dc.subjecteEF-2K
dc.subjecthomology modeling
dc.subjectmolecular docking
dc.subjectmolecular dynamics simulation
dc.titleStructure prediction of eukaryotic elongation factor-2 kinase and identification of the binding mechanisms of its inhibitors: homology modeling, molecular docking, and molecular dynamics simulation
dc.typeArticle

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