An in silico study of how histone tail conformation affects the binding affinity of ING family proteins
Background 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...
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PeerJ Inc.
2022-09-01
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| _version_ | 1797418997600223232 |
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| author | Nadir Gül Ahmet Yıldız |
| author_facet | Nadir Gül Ahmet Yıldız |
| author_sort | Nadir Gül |
| collection | DOAJ |
| description | Background 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 protein-protein 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 protein-protein 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. |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:42:07Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-3bce0ea8af4a4fd68a97b281881cc5212023-12-03T10:47:40ZengPeerJ Inc.PeerJ2167-83592022-09-0110e1402910.7717/peerj.14029An in silico study of how histone tail conformation affects the binding affinity of ING family proteinsNadir Gül0Ahmet Yıldız1Faculty of Natural Sciences, Turkish-German University, Istanbul, TurkeyFaculty of Engineering, Turkish-German University, Istanbul, TurkeyBackground 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 protein-protein 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 protein-protein 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.https://peerj.com/articles/14029.pdfEpigeneticsHistone TailING ProteinIn silicoBinding affinityMolecular docking |
| spellingShingle | Nadir Gül Ahmet Yıldız An in silico study of how histone tail conformation affects the binding affinity of ING family proteins PeerJ Epigenetics Histone Tail ING Protein In silico Binding affinity Molecular docking |
| title | An in silico study of how histone tail conformation affects the binding affinity of ING family proteins |
| title_full | An in silico study of how histone tail conformation affects the binding affinity of ING family proteins |
| title_fullStr | An in silico study of how histone tail conformation affects the binding affinity of ING family proteins |
| title_full_unstemmed | An in silico study of how histone tail conformation affects the binding affinity of ING family proteins |
| title_short | An in silico study of how histone tail conformation affects the binding affinity of ING family proteins |
| title_sort | in silico study of how histone tail conformation affects the binding affinity of ing family proteins |
| topic | Epigenetics Histone Tail ING Protein In silico Binding affinity Molecular docking |
| url | https://peerj.com/articles/14029.pdf |
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