On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structures

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• dc.contributor.author Marín López, Manuel Alejandro, 1987-ca
• dc.contributor.author Planas Iglesias, Joan, 1980-ca
• dc.contributor.author Aguirre Plans, Joaquim, 1993-ca
• dc.contributor.author Bonet Martínez, Jaume, 1982-ca
• dc.contributor.author García-García, Javier, 1982-ca
• dc.contributor.author Fernández Fuentes, Narcísca
• dc.contributor.author Oliva Miguel, Baldomeroca
• dc.date.accessioned 2018-04-11T07:28:16Z
• dc.date.available 2018-04-11T07:28:16Z
• dc.date.issued 2018
• dc.description.abstract 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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Marín-López MA, Planas-Iglesias J, Aguirre-Plans J, Bonet J, Garcia-Garcia J, Fernandez-Fuentes N et al. On the mechanisms of protein interactions: predicting their affinity from unbound tertiary structures. Bioinformatics. 2018 Feb 15;34(4):592-8. DOI: 10.1093/bioinformatics/btx616
• dc.identifier.doi http://dx.doi.org/10.1093/bioinformatics/btx616
• dc.identifier.issn 1367-4803
• dc.identifier.uri http://hdl.handle.net/10230/34332
• dc.language.iso eng
• dc.publisher Oxford University Pressca
• dc.relation.ispartof Bioinformatics. 2018 Feb 15;34(4):592-8
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-57518-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2011-22568
• dc.rights © 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.com
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword BADock
• dc.subject.keyword Binding affinity predictor
• dc.subject.keyword Mechanisms of protein interactions
• dc.title On the mechanisms of protein interactions: Predicting their affinity from unbound tertiary structuresca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion