An in silico study of how histone tail conformation affects the binding affinity of ING family proteins

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dc.authoridGUL, Nadir/0000-0003-1259-4910
dc.contributor.authorGül, Nadir
dc.contributor.authorYildiz, Ahmet
dc.date.accessioned2025-02-20T08:40:09Z
dc.date.available2025-02-20T08:40:09Z
dc.date.issued2022
dc.departmentTürk-Alman Üniversitesien_US
dc.description.abstractBackground. Due to its intrinsically disordered nature, the histone tail is conformationally heterogenic. Therefore, it provides specific binding sites for different binding proteins or factors through reversible post-translational modifications (PTMs). For instance, experimental studies stated that the ING family binds with the histone tail that has methylation on the lysine in position 4. However, numerous complexes featuring a methylated fourth lysine residue of the histone tail can be found in the UniProt database. So the question arose if other factors like the conformation of the histone tail affect the binding affinity. Methods. The crystal structure of the PHD finger domain from the proteins ING1, ING2, ING4, and ING5 are docked to four histone H3 tails with two different conformations using Haddock 2.4 and ClusPro. The best four models for each combination are selected and a two-sample t-test is performed to compare the binding affinities of helical conformations vs. linear conformations using Prodigy. The proteinprotein interactions are examined using LigPlot. Results. The linear histone conformations in predicted INGs-histone H3 complexes exhibit statistically significant higher binding affinity than their helical counterparts (confidence level of 99%). The outputs of predicted models generated by the molecular docking programs Haddock 2.4 and ClusPro are comparable, and the obtained proteinprotein interaction patterns are consistent with experimentally confirmed binding patterns. Conclusion. The results show that the conformation of the histone tail is significantly affecting the binding affinity of the docking protein. Herewith, this in silico study demonstrated in detail the binding preference of the ING protein family to histone H3 tail. Further research on the effect of certain PTMs on the final tail conformation and the interaction between those factors seem to be promising for a better understanding of epigenetics.
dc.identifier.doi10.7717/peerj.14029
dc.identifier.issn2167-8359
dc.identifier.pmid36199288
dc.identifier.scopus2-s2.0-85139714251
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.7717/peerj.14029
dc.identifier.urihttps://hdl.handle.net/20.500.12846/1554
dc.identifier.volume10en_US
dc.identifier.wosWOS:000896031100001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPeerj Inc
dc.relation.ispartofPeerj
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250220
dc.subjectEpigeneticsen_US
dc.subjectHistone Tailen_US
dc.subjectING Proteinen_US
dc.subjectIn silicoen_US
dc.subjectBinding affinityen_US
dc.subjectMolecular dockingen_US
dc.subjectIntrinsically Disordered Proteinsen_US
dc.titleAn in silico study of how histone tail conformation affects the binding affinity of ING family proteins
dc.typeArticle

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