2×2 GG/GG internal loops are highly dynamic, which is probably one of the reasons why structural studies were not performed. Inspired by the discovery of a small molecule, CB253, (Figure ) which reorganizes the conformation of r(G4C2) exp to have 2×2 GG/GG internal loops rather than 1×1 G/G, we investigated the conformational landscape adopted by 2×2 GG/GG internal loops using both NMR methods and MD calculations.