Novel Computational/Experimental Apporaches to DNA/Proteins Interactions

Studying the interaction of Rad51 and ssDNA is very challenging since, the fact that the relevant supramolecular assemblies are often very stable, the intrinsic flexibility of ssDNA and the geometrical/energetic features of resulting interface concur to increase the complexity of the system under investigation. Yet, in this context, multiscale molecular simulations appear as a unique instrument for studying DNA–protein interactions, owing to its atomistic resolution and capability of mimicking the considered biological environment (i.e., explicit solvent, temperature, and physiological/imposed ionic strength). In order to get a comprehensive structural and thermodynamic perspective of Rad51/ssDNA interaction, in this work we propose to apply large scale, parallel atomistic and coarse-grained (CG) simulations, coupled with high resolution imaging techniques and biophysical methods to i) dissect the docking mode of Rad51 to ssDNA, ii) deriving the energetics of the interface in the protein/nucleic acid interface, iii) uncovering the role of DNA and protein flexibility in their assembly formation, and iv) determining the mechanism of Rad51 binding to ssDNA.