Crystallographic structure versus homology model: a case study of molecular dynamics simulation of human and zebrafish histone deacetylase 10

dc.contributor.authorYelekçi, Kemal
dc.contributor.authorYelekçi, Kemal
dc.date.accessioned2020-10-07T11:56:58Zen_US
dc.date.available2020-10-07T11:56:58Zen_US
dc.date.issued2020en_US
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
dc.description.abstractHistone deacetylase (HDAC) 10 has been implicated in the pathology of various cancers and neurodegenerative disorders, making the discovery of novel inhibitors of the isoform an important endeavor. However, the unavailability of crystallographic structure of human HDAC10 (hHDAC10) hinders structure-based drug design effort. Previously, we reported the homology modeled structure of human HDAC10 built using the crystallographic structure of Danio rerio (zebrafish) HDAC10 (zHDAC10) (Protein Data Bank (PDB) ID; 5TD7, released on 24 May 2017) as a template. Here, in continuation with our study, both hHDAC10 and zHDAC10, and their respective complexes with trichostatin A (TSA), quisinostat, and the native ligand (in 5TD7), 7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptane-2,2-diol (PDB ID; FKS) were submitted to 100 ns-long unrestrained molecular dynamics (MD) simulations. Comparative analyses of the MD trajectories revealed that zHDAC10 and its complexes displayed higher stability than hHDAC10 and its corresponding complexes over time. Nonetheless, docking of active and inactive set molecules revealed that more reliable conformations of hHDAC10 could be obtained at an extended time period. This study may shed more light on the reliability of hHDAC10 modeled structure for use in selective inhibitor design.Communicated by Ramaswamy H. Sarma.en_US
dc.identifier.citation14
dc.identifier.doi10.1080/07391102.2019.1691658en_US
dc.identifier.endpage4406en_US
dc.identifier.issue38en_US
dc.identifier.pmid31701819en_US
dc.identifier.scopus2-s2.0-85075165503en_US
dc.identifier.scopusqualityN/A
dc.identifier.startpage4397en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/3473
dc.identifier.urihttps://doi.org/10.1080/07391102.2019.1691658
dc.identifier.volume15en_US
dc.identifier.wosWOS:000496636800001en_US
dc.identifier.wosqualityN/A
dc.institutionauthorYelekçi, Kemalen_US
dc.language.isoenen_US
dc.publisherTaylor & Francisen_US
dc.relation.journalJournal of Biomolecular Structure and Dynamicsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectMD simulationen_US
dc.subjecthHDAC10en_US
dc.subjectKnown inhibitorsen_US
dc.subjectzHDAC10en_US
dc.titleCrystallographic structure versus homology model: a case study of molecular dynamics simulation of human and zebrafish histone deacetylase 10en_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

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