The research team of Modelling and Simulation of nucleic acids concentrates its efforts on detemining the rules that governs the process of the RNA folding. The techniques used and the major results obtained are as follows :
Simulations of molecular and Brownian dynamics (MD) with RNA fragments alone or in interaction with cationic ligands (magnesium ions or antibiotics). Achievement of the first stable trajectories in aqueous environment, in the presence of counter-ions, using the Ewald method. Roles of the H bonds implicating C-H bonds in the RNA. Use of Brownian dynamics to predict binding sites for magnesium ions and cationic ligands.
Building and modelling of RNA three-dimensional structures based on chemical and enzymatic probing, together with other teams of the Research Unit. Structural and functional studies with sequence alignments and mutagenesis of the catalytic RNA. Complete modelling of several group I introns, for example the intron of Tetrahymena thermophila. Modelling of the RNase P RNA of two important eubacterial classes. The effects in vitro and in vivo of many mutations in a catalytic intron have been analyzed.
Development of bioinformatic tools allowing the search for covariations or the 3D modelling of nucleic acids. Several computer programs for analysing and modelling RNA have been developed in the laboratory : COSEQ (covariation search); MANIP (modular building of RNA); DRAWNA (drawing of complex structures of RNA). These programs have for example been used to identify the recurrent 5S Loop E motif in other structured RNA.
Crystallogenesis of RNA fragments incorporating binding sites for small molecules (for example antibiotics) or endowed with catalytic activity. A nonamer has been crystallized and its structure has been solved at a high resolution (0.97 ?). It reveals a sulfate ion sequestered by three GoU pairs.
Use of Darwinian selection in vitro to isolate a universal ligase formed by pre-existing modules. The approaches mentioned in the summary are situated at different levels of complexity. However, used together, they enable us to visualize at the appropriate level the structures adopted by RNA in space, to better understand their biological functioning and to relate the biological evolution of RNA to the structural and dynamic properties of the four nucleic acid bases. This knowledge should further allow the understanding of the interactions between RNA and proteins, and especially the interactions between RNA and antibiotics or other small organic molecules targeting specific RNA motifs.