To carry out their activities, Research Teams of the Frédéric Joliot Institute for Life Sciences have developed high-profile technological platforms in many areas : biomedical imaging, structural biology, metabolomics, High-Throughput screening, level 3 microbiological safety laboratory...
Within the Institute, the "Funding Research and Technology Transfer" team is at your disposal to identify the scientists and the skills you need to set up a joint project, to define the terms of a collaboration contract or study.
Whether you are an academic, a SME or an industrialist, our team informs and advices you about the possibilities of consortium assembly, technology transfer, patent licensing or use of our platforms.
The team is also at the disposal of the researchers of the institute to accompany them in achieving their valorization objectives.
Scientific result | Structural biology
Researchers at I2BC/CEA-Joliot, in collaboration with the RPBS platform, have developed the third version of their InterEvDock server for structural modelling of protein-protein interactions. The server integrates new algorithms for exploiting sequence evolution information. This greatly improves its performance for the generation of correct assembly models.
Predicting the structure of proteins and their interaction modes is a real challenge for structural biologists. In addition to the gap between the number of proteins whose sequence is known and the number of available structures, proteomics has recently revealed the previously hidden part of the iceberg: hundreds of thousands of physical interactions between proteins. Knowing the surfaces involved in these interactions is essential, not only for understanding the mechanisms that govern how cells and organisms function, but also for designing new therapeutic or enzymatic molecules for pharmaceutical and biotechnological purposes.
Jessica Andreani and Raphaël Guérois (Team “Molecular Assemblies and Genome Integrity”/LBSR/I2BC) have been working for several years on the modelling of protein-protein interactions. In particular, they contribute to the improvement of prediction methods by integrating an evolutionary dimension into molecular docking tools. Indeed, protein interfaces tend to be more conserved than other regions on the protein surface. Moreover, signs of co-evolution can be detected at interfaces, where potentially disruptive mutations are compensated for by mutations in contacting positions on the protein partner. The team has thus developed and released the InterEvDock server, in collaboration with the Ressource Parisienne en Bioinformatique Structurale (RPBS, University of Paris). As in previous versions, the InterEvDock3 server offers a systematic search for possible interfaces between two partners (known as free docking) and generates numerous conformations that are then ranked, in particular by taking into account information on the evolution of protein sequences. This unique modelling server processes user requests in a variety of formats (structural or sequence data, on one or both partners).
The software is now in its third version (InterEvDock3). This version integrates three new prediction modes that are described in two articles published in
Bioinformatics2. The first mode, which is not based on free docking, allows homology modelling of large complexes with potentially low sequence identity. It uses sequences (no structures) as input and runs a template-based modelling protocol by searching exhaustively for close and distant homologs to generate assembly models.
The second mode predicts the structure of complexes from contact maps resulting from methods combining covariation analysis and deep learning. This mode uses 3D structures of monomers or homomultimers (such as a helicase hexamer) to perform a free docking approach while trying to satisfy the contacts predicted in the contact map. It is able to handle some ambiguous information, especially if one of the two partners is a homomultimer (with its residues thus present several times in the structure) and a contact in the predicted map can thus materialise in different ways.
Finally, the third mode uses 3D structures of monomers or multimeric complexes (possibly modelled from sequences by mode 1) and implements a new strategy for evaluating interfaces with coevolutionary information. Ten to forty representative pairs of homologous sequences (i.e. ten to forty evolutionarily conserved interactions between homologs) are selected, modelled at the atomic scale and scored. This new algorithm, tested on a database of 752 complexes (see Bioinformatics2), increases the number of correctly predicted complexes by 30%.
It usually takes between 20 and 60 minutes for the server to propose an interaction model. Developed with funding from two national health and biology infrastructures (FRISBI and IFB), the server is accessible from the RPBS platform: https://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock3/
Chloé Quignot, Guillaume Postic,
Hélène Bret, Julien Rey,
Pierre Granger, Samuel Murail, Pablo Chacón,
Jessica Andreani*, Pierre Tufféry* and
InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps. |
Nucleic Acids Res, 2021 May 12;gkab358.
Pierre Granger, Pablo Chacón,
Atomic-level evolutionary information improves protein-protein interface scoring. |
Bioinformatics, 2021 Apr 26;btab254.
Jessica Andreani, Julien Marcoux, Victor Reys,
Raphaël Guerois, Julien Rey, Emmanuelle Mouton-Barbosa, Yves Vandenbrouck, Sarah Cianferani, Odile Burlet-Schiltz, Gilles Labesse , Pierre Tufféry. Proteo3Dnet: a web server for the integration of structural information with interactomics data. |
Nucleic Acids Res, 2021 May 8;gkab332.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.