Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.
An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5634604?pdf=render |
| _version_ | 1819062654579245056 |
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| author | Stefan M Ivanov Andrew Cawley Roland G Huber Peter J Bond Jim Warwicker |
| author_facet | Stefan M Ivanov Andrew Cawley Roland G Huber Peter J Bond Jim Warwicker |
| author_sort | Stefan M Ivanov |
| collection | DOAJ |
| description | An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. |
| first_indexed | 2024-12-21T15:02:13Z |
| format | Article |
| id | doaj.art-3d614f4708f94dacbf8ad91b0eaf47c8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T15:02:13Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3d614f4708f94dacbf8ad91b0eaf47c82022-12-21T18:59:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011210e018592810.1371/journal.pone.0185928Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.Stefan M IvanovAndrew CawleyRoland G HuberPeter J BondJim WarwickerAn improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.http://europepmc.org/articles/PMC5634604?pdf=render |
| spellingShingle | Stefan M Ivanov Andrew Cawley Roland G Huber Peter J Bond Jim Warwicker Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. PLoS ONE |
| title | Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. |
| title_full | Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. |
| title_fullStr | Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. |
| title_full_unstemmed | Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. |
| title_short | Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold. |
| title_sort | protein protein interactions in paralogues electrostatics modulates specificity on a conserved steric scaffold |
| url | http://europepmc.org/articles/PMC5634604?pdf=render |
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