Construction of Histone–Protein Complex Structures by Peptide Growing
The structures of histone complexes are master keys to epigenetics. Linear histone peptide tails often bind to shallow pockets of reader proteins via weak interactions, rendering their structure determination challenging. In the present study, a new protocol, PepGrow, is introduced. PepGrow uses doc...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13831 |
| _version_ | 1797579770980990976 |
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| author | Balázs Zoltán Zsidó Bayartsetseg Bayarsaikhan Rita Börzsei Csaba Hetényi |
| author_facet | Balázs Zoltán Zsidó Bayartsetseg Bayarsaikhan Rita Börzsei Csaba Hetényi |
| author_sort | Balázs Zoltán Zsidó |
| collection | DOAJ |
| description | The structures of histone complexes are master keys to epigenetics. Linear histone peptide tails often bind to shallow pockets of reader proteins via weak interactions, rendering their structure determination challenging. In the present study, a new protocol, PepGrow, is introduced. PepGrow uses docked histone fragments as seeds and grows the full peptide tails in the reader-binding pocket, producing atomic-resolution structures of histone–reader complexes. PepGrow is able to handle the flexibility of histone peptides, and it is demonstrated to be more efficient than linking pre-docked peptide fragments. The new protocol combines the advantages of popular program packages and allows fast generation of solution structures. AutoDock, a force-field-based program, is used to supply the docked peptide fragments used as structural seeds, and the building algorithm of Modeller is adopted and tested as a peptide growing engine. The performance of PepGrow is compared to ten other docking methods, and it is concluded that in situ growing of a ligand from a seed is a viable strategy for the production of complex structures of histone peptides at atomic resolution. |
| first_indexed | 2024-03-10T22:41:41Z |
| format | Article |
| id | doaj.art-e452991f19f04b3da6363987129c7963 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:41:41Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e452991f19f04b3da6363987129c79632023-11-19T11:03:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181383110.3390/ijms241813831Construction of Histone–Protein Complex Structures by Peptide GrowingBalázs Zoltán Zsidó0Bayartsetseg Bayarsaikhan1Rita Börzsei2Csaba Hetényi3Pharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti Út 12, 7624 Pécs, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti Út 12, 7624 Pécs, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti Út 12, 7624 Pécs, HungaryPharmacoinformatics Unit, Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti Út 12, 7624 Pécs, HungaryThe structures of histone complexes are master keys to epigenetics. Linear histone peptide tails often bind to shallow pockets of reader proteins via weak interactions, rendering their structure determination challenging. In the present study, a new protocol, PepGrow, is introduced. PepGrow uses docked histone fragments as seeds and grows the full peptide tails in the reader-binding pocket, producing atomic-resolution structures of histone–reader complexes. PepGrow is able to handle the flexibility of histone peptides, and it is demonstrated to be more efficient than linking pre-docked peptide fragments. The new protocol combines the advantages of popular program packages and allows fast generation of solution structures. AutoDock, a force-field-based program, is used to supply the docked peptide fragments used as structural seeds, and the building algorithm of Modeller is adopted and tested as a peptide growing engine. The performance of PepGrow is compared to ten other docking methods, and it is concluded that in situ growing of a ligand from a seed is a viable strategy for the production of complex structures of histone peptides at atomic resolution.https://www.mdpi.com/1422-0067/24/18/13831dockinghistonepeptideligandfragmentgrowing |
| spellingShingle | Balázs Zoltán Zsidó Bayartsetseg Bayarsaikhan Rita Börzsei Csaba Hetényi Construction of Histone–Protein Complex Structures by Peptide Growing International Journal of Molecular Sciences docking histone peptide ligand fragment growing |
| title | Construction of Histone–Protein Complex Structures by Peptide Growing |
| title_full | Construction of Histone–Protein Complex Structures by Peptide Growing |
| title_fullStr | Construction of Histone–Protein Complex Structures by Peptide Growing |
| title_full_unstemmed | Construction of Histone–Protein Complex Structures by Peptide Growing |
| title_short | Construction of Histone–Protein Complex Structures by Peptide Growing |
| title_sort | construction of histone protein complex structures by peptide growing |
| topic | docking histone peptide ligand fragment growing |
| url | https://www.mdpi.com/1422-0067/24/18/13831 |
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