On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures
MOTIVATION: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/34332 |
| Acceso en línea: | http://hdl.handle.net/10230/34332 http://dx.doi.org/10.1093/bioinformatics/btx616 |
| Access Level: | acceso abierto |
| Palabra clave: | BADock Binding affinity predictor Mechanisms of protein interactions |
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On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structuresMarín López, Manuel Alejandro, 1987-Planas Iglesias, Joan, 1980-Aguirre Plans, Joaquim, 1993-Bonet Martínez, Jaume, 1982-García-García, Javier, 1982-Fernández Fuentes, NarcísOliva Miguel, BaldomeroBADockBinding affinity predictorMechanisms of protein interactionsMOTIVATION: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing the dimensionality of the search process. The association rate for the formation of such complex plays a crucial role in the cell biology and depends on how the partners diffuse to be close to each other. Predicting the binding free energy of proteins provides new opportunities to modulate and control protein-protein interactions. However, existing methods require the 3D structure of the complex to predict its affinity, severely limiting their application to interactions with known structures. RESULTS: We present a new approach that relies on the unbound protein structures and protein docking to predict protein-protein binding affinities. Through the study of the docking space (i.e. decoys), the method predicts the binding affinity of the query proteins when the actual structure of the complex itself is unknown. We tested our approach on a set of globular and soluble proteins of the newest affinity benchmark, obtaining accuracy values comparable to other state-of-art methods: a 0.4 correlation coefficient between the experimental and predicted values of ΔG and an error < 3 Kcal/mol. AVAILABILITY AND IMPLEMENTATION: The binding affinity predictor is implemented and available at http://sbi.upf.edu/BADock and https://github.com/badocksbi/BADock. CONTACT: j.planas-iglesias@warwick.ac.uk or baldo.oliva@upf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.The work has been supported by grants BIO2014-57518-R and BIO2011-22568 of the Spanish Ministry of Economy (MINECO), INB 2015-2017 of ISCIII, and 2014SGR1161 of Generalitat de Catalunya.Oxford University Press201820182018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/34332http://dx.doi.org/10.1093/bioinformatics/btx616reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésBioinformatics. 2018 Feb 15;34(4):592-8info:eu-repo/grantAgreement/ES/1PE/BIO2014-57518-Rinfo:eu-repo/grantAgreement/ES/3PN/BIO2011-22568© The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/343322026-06-12T07:21:37Z |
| dc.title.none.fl_str_mv |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| title |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| spellingShingle |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures Marín López, Manuel Alejandro, 1987- BADock Binding affinity predictor Mechanisms of protein interactions |
| title_short |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| title_full |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| title_fullStr |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| title_full_unstemmed |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| title_sort |
On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures |
| dc.creator.none.fl_str_mv |
Marín López, Manuel Alejandro, 1987- Planas Iglesias, Joan, 1980- Aguirre Plans, Joaquim, 1993- Bonet Martínez, Jaume, 1982- García-García, Javier, 1982- Fernández Fuentes, Narcís Oliva Miguel, Baldomero |
| author |
Marín López, Manuel Alejandro, 1987- |
| author_facet |
Marín López, Manuel Alejandro, 1987- Planas Iglesias, Joan, 1980- Aguirre Plans, Joaquim, 1993- Bonet Martínez, Jaume, 1982- García-García, Javier, 1982- Fernández Fuentes, Narcís Oliva Miguel, Baldomero |
| author_role |
author |
| author2 |
Planas Iglesias, Joan, 1980- Aguirre Plans, Joaquim, 1993- Bonet Martínez, Jaume, 1982- García-García, Javier, 1982- Fernández Fuentes, Narcís Oliva Miguel, Baldomero |
| author2_role |
author author author author author author |
| dc.subject.none.fl_str_mv |
BADock Binding affinity predictor Mechanisms of protein interactions |
| topic |
BADock Binding affinity predictor Mechanisms of protein interactions |
| description |
MOTIVATION: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing the dimensionality of the search process. The association rate for the formation of such complex plays a crucial role in the cell biology and depends on how the partners diffuse to be close to each other. Predicting the binding free energy of proteins provides new opportunities to modulate and control protein-protein interactions. However, existing methods require the 3D structure of the complex to predict its affinity, severely limiting their application to interactions with known structures. RESULTS: We present a new approach that relies on the unbound protein structures and protein docking to predict protein-protein binding affinities. Through the study of the docking space (i.e. decoys), the method predicts the binding affinity of the query proteins when the actual structure of the complex itself is unknown. We tested our approach on a set of globular and soluble proteins of the newest affinity benchmark, obtaining accuracy values comparable to other state-of-art methods: a 0.4 correlation coefficient between the experimental and predicted values of ΔG and an error < 3 Kcal/mol. AVAILABILITY AND IMPLEMENTATION: The binding affinity predictor is implemented and available at http://sbi.upf.edu/BADock and https://github.com/badocksbi/BADock. CONTACT: j.planas-iglesias@warwick.ac.uk or baldo.oliva@upf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018 2018 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/34332 http://dx.doi.org/10.1093/bioinformatics/btx616 |
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http://hdl.handle.net/10230/34332 http://dx.doi.org/10.1093/bioinformatics/btx616 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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Bioinformatics. 2018 Feb 15;34(4):592-8 info:eu-repo/grantAgreement/ES/1PE/BIO2014-57518-R info:eu-repo/grantAgreement/ES/3PN/BIO2011-22568 |
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http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Oxford University Press |
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Oxford University Press |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Repositorio Digital de la UPF |
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