Protein-assisted RNA fragment docking (RnaX) for modeling RNA-protein interactions using ModelX

Delgado Blanco, Javier; Radusky, Leandro; Cianferoni, Damiano; Serrano Pubull, Luis, 1982-

Protein-assisted RNA fragment docking (RnaX) for modeling RNA-protein interactions using ModelX

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dc.contributor.author Delgado Blanco, Javier
dc.contributor.author Radusky, Leandro
dc.contributor.author Cianferoni, Damiano
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.date.accessioned 2020-04-07T08:47:56Z
dc.date.available 2020-04-07T08:47:56Z
dc.date.issued 2019
dc.description.abstract RNA-protein interactions are crucial for such key biological processes as regulation of transcription, splicing, translation, and gene silencing, among many others. Knowing where an RNA molecule interacts with a target protein and/or engineering an RNA molecule to specifically bind to a protein could allow for rational interference with these cellular processes and the design of novel therapies. Here we present a robust RNA-protein fragment pair-based method, termed RnaX, to predict RNA-binding sites. This methodology, which is integrated into the ModelX tool suite (http://modelx.crg.es), takes advantage of the structural information present in all released RNA-protein complexes. This information is used to create an exhaustive database for docking and a statistical forcefield for fast discrimination of true backbone-compatible interactions. RnaX, together with the protein design forcefield FoldX, enables us to predict RNA-protein interfaces and, when sufficient crystallographic information is available, to reengineer the interface at the sequence-specificity level by mimicking those conformational changes that occur on protein and RNA mutagenesis. These results, obtained at just a fraction of the computational cost of methods that simulate conformational dynamics, open up perspectives for the engineering of RNA-protein interfaces.
dc.description.sponsorship This work was supported by funding from the Spanish Ministry of Economy, Industry, and Competitiveness (Plan Nacional BFU2015-63571-P), the Centro de Excelencia Severo Ochoa, and the Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya. The project that gave rise to these results was supported by a fellowship from “la Caixa” Foundation (ID 100010434; fellowship code LCF/BQ/DI19/11730061).
dc.format.mimetype application/pdf
dc.identifier.citation Delgado Blanco J, Radusky LG, Cianferoni D, Serrano L. Protein-assisted RNA fragment docking (RnaX) for modeling RNA-protein interactions using ModelX. Proc Natl Acad Sci U S A. 2019; 116(49):24568-73. DOI: 10.1073/pnas.1910999116
dc.identifier.doi http://dx.doi.org/10.1073/pnas.1910999116
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10230/44178
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A. 2019; 116(49):24568-73
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-63571-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword FoldX
dc.subject.keyword ModelX
dc.subject.keyword RNA docking
dc.subject.keyword Protein–RNA interface design
dc.subject.keyword Protein–RNA interface engineering
dc.title Protein-assisted RNA fragment docking (RnaX) for modeling RNA-protein interactions using ModelX
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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