Contacts-based prediction of binding affinity in protein–protein complexes
Almost all critical functions in cells rely on specific protein–protein interactions. Understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack a thorough understanding of the energetics of association of proteins. Here, we introduce...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/07454 |
| _version_ | 1828375040723255296 |
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| author | Anna Vangone Alexandre MJJ Bonvin |
| author_facet | Anna Vangone Alexandre MJJ Bonvin |
| author_sort | Anna Vangone |
| collection | DOAJ |
| description | Almost all critical functions in cells rely on specific protein–protein interactions. Understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack a thorough understanding of the energetics of association of proteins. Here, we introduce a new and simple approach to predict binding affinity based on functional and structural features of the biological system, namely the network of interfacial contacts. We assess its performance against a protein–protein binding affinity benchmark and show that both experimental methods used for affinity measurements and conformational changes have a strong impact on prediction accuracy. Using a subset of complexes with reliable experimental binding affinities and combining our contacts and contact-types-based model with recent observations on the role of the non-interacting surface in protein–protein interactions, we reach a high prediction accuracy for such a diverse dataset outperforming all other tested methods. |
| first_indexed | 2024-04-14T07:42:18Z |
| format | Article |
| id | doaj.art-908b06975b2247a2b97bfe4702528581 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:42:18Z |
| publishDate | 2015-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-908b06975b2247a2b97bfe47025285812022-12-22T02:05:27ZengeLife Sciences Publications LtdeLife2050-084X2015-07-01410.7554/eLife.07454Contacts-based prediction of binding affinity in protein–protein complexesAnna Vangone0Alexandre MJJ Bonvin1https://orcid.org/0000-0001-7369-1322Computational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science—Chemistry, Utrecht University, Utrecht, NetherlandsComputational Structural Biology Group, Bijvoet Center for Biomolecular Research, Faculty of Science—Chemistry, Utrecht University, Utrecht, NetherlandsAlmost all critical functions in cells rely on specific protein–protein interactions. Understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack a thorough understanding of the energetics of association of proteins. Here, we introduce a new and simple approach to predict binding affinity based on functional and structural features of the biological system, namely the network of interfacial contacts. We assess its performance against a protein–protein binding affinity benchmark and show that both experimental methods used for affinity measurements and conformational changes have a strong impact on prediction accuracy. Using a subset of complexes with reliable experimental binding affinities and combining our contacts and contact-types-based model with recent observations on the role of the non-interacting surface in protein–protein interactions, we reach a high prediction accuracy for such a diverse dataset outperforming all other tested methods.https://elifesciences.org/articles/07454protein-protein complexbinding affinityprotein contactburied surface areaprotein-protein interactionnon-interacting surface |
| spellingShingle | Anna Vangone Alexandre MJJ Bonvin Contacts-based prediction of binding affinity in protein–protein complexes eLife protein-protein complex binding affinity protein contact buried surface area protein-protein interaction non-interacting surface |
| title | Contacts-based prediction of binding affinity in protein–protein complexes |
| title_full | Contacts-based prediction of binding affinity in protein–protein complexes |
| title_fullStr | Contacts-based prediction of binding affinity in protein–protein complexes |
| title_full_unstemmed | Contacts-based prediction of binding affinity in protein–protein complexes |
| title_short | Contacts-based prediction of binding affinity in protein–protein complexes |
| title_sort | contacts based prediction of binding affinity in protein protein complexes |
| topic | protein-protein complex binding affinity protein contact buried surface area protein-protein interaction non-interacting surface |
| url | https://elifesciences.org/articles/07454 |
| work_keys_str_mv | AT annavangone contactsbasedpredictionofbindingaffinityinproteinproteincomplexes AT alexandremjjbonvin contactsbasedpredictionofbindingaffinityinproteinproteincomplexes |