Section: Application Domains

Protein-RNA Interactions

Participants : Isaure Chauvot de Beauchêne [contact person] , Bernard Maigret, Maria Elisa Ruiz Echartea, David Ritchie.

As well as playing an essential role in the translation of DNA into proteins, RNA molecules carry out many other essential biological functions in cells, often through their interactions with proteins. A critical challenge in modelling such interactions computationally is that the RNA is often highly flexible, especially in single-stranded (ssRNA) regions of its structure. These flexible regions are often very important because it is through their flexibility that the RNA can adjust its 3D conformation in order to bind to a protein surface. However, conventional protein-protein docking algorithms generally assume that the 3D structures to be docked are rigid, and so are not suitable for modeling protein-RNA interactions. There is therefore much interest in developing protein-RNA docking algorithms which can take RNA flexibility into account.

We are currently developing a novel flexible docking algorithm which first docks small fragments of ssRNA (typically three nucleotides at a time) onto a protein surface, and then combinatorially reassembles those fragments in order to recover a contiguous ssRNA structure on the protein surface [33], [32]. We have since implemented a prototype “forward-backward” dynamic programming algorithm with stochastic backtracking that allows us to model protein RNA interactions for ssRNAs of up to 7 nucleotides without requiring any prior knowledge of the interaction, while still avoiding a brute-force search. In the frame of our PEPS collaboration “InterANRIL” with the IMoPA lab (Univ de Lorraine), we are currently working with biologists to apply the approach to modeling certain long non-coding RNA (lncRNA) complexes. We next plan to build a large library of RNA fragments in order to extend this approach to partially structured RNA molecules, and in the longer term we aim to apply this approach to modeling flexible peptide-protein interactions in a similar way.