Protein-protein binding supersites.
The lack of a deep understanding of how proteins interact remains an important roadblock in advancing efforts to identify binding partners and uncover the corresponding regulatory mechanisms of the functions they mediate. Understanding protein-protein interactions is also essential for designing spe...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1006704 |
| _version_ | 1818516670248910848 |
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| author | Raji Viswanathan Eduardo Fajardo Gabriel Steinberg Matthew Haller Andras Fiser |
| author_facet | Raji Viswanathan Eduardo Fajardo Gabriel Steinberg Matthew Haller Andras Fiser |
| author_sort | Raji Viswanathan |
| collection | DOAJ |
| description | The lack of a deep understanding of how proteins interact remains an important roadblock in advancing efforts to identify binding partners and uncover the corresponding regulatory mechanisms of the functions they mediate. Understanding protein-protein interactions is also essential for designing specific chemical modifications to develop new reagents and therapeutics. We explored the hypothesis of whether protein interaction sites serve as generic biding sites for non-cognate protein ligands, just as it has been observed for small-molecule-binding sites in the past. Using extensive computational docking experiments on a test set of 241 protein complexes, we found that indeed there is a strong preference for non-cognate ligands to bind to the cognate binding site of a receptor. This observation appears to be robust to variations in docking programs, types of non-cognate protein probes, sizes of binding patches, relative sizes of binding patches and full-length proteins, and the exploration of obligate and non-obligate complexes. The accuracy of the docking scoring function appears to play a role in defining the correct site. The frequency of interaction of unrelated probes recognizing the binding interface was utilized in a simple prediction algorithm that showed accuracy competitive with other state of the art methods. |
| first_indexed | 2024-12-11T00:45:19Z |
| format | Article |
| id | doaj.art-de5ca3523ca14cd9a4c4f0a3f0032247 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-11T00:45:19Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-de5ca3523ca14cd9a4c4f0a3f00322472022-12-22T01:26:48ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582019-01-01151e100670410.1371/journal.pcbi.1006704Protein-protein binding supersites.Raji ViswanathanEduardo FajardoGabriel SteinbergMatthew HallerAndras FiserThe lack of a deep understanding of how proteins interact remains an important roadblock in advancing efforts to identify binding partners and uncover the corresponding regulatory mechanisms of the functions they mediate. Understanding protein-protein interactions is also essential for designing specific chemical modifications to develop new reagents and therapeutics. We explored the hypothesis of whether protein interaction sites serve as generic biding sites for non-cognate protein ligands, just as it has been observed for small-molecule-binding sites in the past. Using extensive computational docking experiments on a test set of 241 protein complexes, we found that indeed there is a strong preference for non-cognate ligands to bind to the cognate binding site of a receptor. This observation appears to be robust to variations in docking programs, types of non-cognate protein probes, sizes of binding patches, relative sizes of binding patches and full-length proteins, and the exploration of obligate and non-obligate complexes. The accuracy of the docking scoring function appears to play a role in defining the correct site. The frequency of interaction of unrelated probes recognizing the binding interface was utilized in a simple prediction algorithm that showed accuracy competitive with other state of the art methods.https://doi.org/10.1371/journal.pcbi.1006704 |
| spellingShingle | Raji Viswanathan Eduardo Fajardo Gabriel Steinberg Matthew Haller Andras Fiser Protein-protein binding supersites. PLoS Computational Biology |
| title | Protein-protein binding supersites. |
| title_full | Protein-protein binding supersites. |
| title_fullStr | Protein-protein binding supersites. |
| title_full_unstemmed | Protein-protein binding supersites. |
| title_short | Protein-protein binding supersites. |
| title_sort | protein protein binding supersites |
| url | https://doi.org/10.1371/journal.pcbi.1006704 |
| work_keys_str_mv | AT rajiviswanathan proteinproteinbindingsupersites AT eduardofajardo proteinproteinbindingsupersites AT gabrielsteinberg proteinproteinbindingsupersites AT matthewhaller proteinproteinbindingsupersites AT andrasfiser proteinproteinbindingsupersites |