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Proc Natl Acad Sci U S A. 2019 Dec 3;116(49):24568-24573. doi: 10.1073/pnas.1910999116. Epub 2019 Nov 15.

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

Author information

1
Center for Genomic Regulation, Barcelona Institute for Science and Technology, 08003 Barcelona, Spain.
2
Center for Genomic Regulation, Barcelona Institute for Science and Technology, 08003 Barcelona, Spain; luis.serrano@crg.eu.
3
Universitat Pompeu Fabra, 08002 Barcelona, Spain.
4
Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.

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.

KEYWORDS:

FoldX; ModelX; RNA docking; protein–RNA interface design; protein–RNA interface engineering

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