Homology modeling of human histone deacetylase 10 and design of potential selective inhibitors

dc.contributor.authorYelekçi, Kemal
dc.contributor.authorYelekçi, Kemal
dc.date.accessioned2020-12-13T10:08:53Z
dc.date.available2020-12-13T10:08:53Z
dc.date.issued2019
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
dc.description.abstractHistone deacetylases (HDACs) are implicated in the pathology of various cancers, and their pharmacological blockade has proven to be promising in reversing the malignant phenotypes. However, lack of crystal structures of some of the human HDAC isoforms (e.g., HDAC10) hinders the design of the isoform-selective inhibitor. Here, the recently solved X-ray crystal structure of Danio rerio (zebrafish) HDAC10 (Protein Data Bank (PDB) ID; 5TD7, released on 24 May 2017) was retrieved from the PDB and used as a template structure to model the three-dimensional structure of human HDAC10. The overall quality of the best model (M0017) was assessed by computing its z-score-a measure of the deviation of the total energy of the structure with respect to an energy distribution derived from random conformations and by docking of known HDAC10 inhibitors to its catalytic cavity. Furthermore, to identify potential HDAC10-selective inhibitor ligand-based virtual screening was carried out against the ZINC database. The free modeled structure of HDAC10 and its complexes with quisinostat and the highest-ranked compound ZINC19749069 were submitted to molecular dynamics simulation. The comparative analysis of root-mean-squared deviation, root-mean-squared fluctuation, radius of gyration (Rg), and potential energy of these systems showed that HDAC10-ZINC19749069 complex remained the most stable over time. Thus, M0017 could be potentially used for structure-based inhibitor against HDAC10, and ZINC19749069 may provide a scaffold for further optimization. Communicated by Ramaswamy H. Sarmaen_US
dc.description.sponsorshipEPICHEM Bayero University Kano's "Needs Assessment Grant"en_US
dc.identifier.citation25
dc.identifier.doi10.1080/07391102.2018.1521747en_US
dc.identifier.endpage3636en_US
dc.identifier.issn0739-1102en_US
dc.identifier.issn1538-0254en_US
dc.identifier.issn0739-1102
dc.identifier.issn1538-0254
dc.identifier.issue14en_US
dc.identifier.pmid30204052en_US
dc.identifier.scopus2-s2.0-85059965941en_US
dc.identifier.scopusqualityQ2
dc.identifier.startpage3627en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/3539
dc.identifier.urihttps://doi.org/10.1080/07391102.2018.1521747
dc.identifier.volume37en_US
dc.identifier.wosWOS:000475917200005en_US
dc.identifier.wosqualityN/A
dc.institutionauthorUba, Abdullahi Ibrahimen_US
dc.institutionauthorYelekçi, Kemalen_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.journalJournal Of Biomolecular Structure & Dynamicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectLigand-based virtual screeningen_US
dc.subjectMolecular dockingen_US
dc.subjectMolecular dynamics simulationen_US
dc.subjectHDAC10-selective inhibitorsen_US
dc.subjectHomology modelingen_US
dc.titleHomology modeling of human histone deacetylase 10 and design of potential selective inhibitorsen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

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