Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses

Cécilia Hognon; Tom Miclot; Cristina Garcia Iriepa; Antonio Francés-Monerris; Stephanie Grandemange; Alessio Terenzi; Marco Marazzi; Giampaolo Barone; Antonio Monari

The equilibrium MD simulations were started placing the G4 in the nearby of the SUD complex and the trajectories evolved yielding two distinct interaction modes, as reported in Figure 2 . In particular, we can easily distinguish between a first mode of binding in which the G4 mainly interacts with only one SUD monomer, called monomeric binding mode, and a second one in which the nucleic acid is firmly placed at the interface between the two protein monomeric subunits, referred as dimeric binding mode. The corresponding root mean square deviations (RMSD) with respect to the initial structure are also reported and globally show that both the RNA and the protein units are stable. As expected, a slightly larger value of the RMSD is observed for the protein, as a consequence of its larger flexibility compared to the rigid G4 structures (Figure 2 d, c). Note also that the slight initial increase of the protein RMSD observed for the dimeric mode is due to the necessity of a slight structural rearrangement to accommodate the G4 in the interaction pocket. Both modes are also globally stable all along the MD trajectory, and no spontaneous release of the G4 is observed. However, at the end of the trajectory the dimeric mode exhibits a slight slipping from the center of the interface area. This is probably due to the relative short length of the oligomer, also in agreement with previous experimental observations. 28 Apart from the different positioning of the G4, other structural evidences can already be surmised from the visual inspection of the MD trajectory. In particular, the SUD dimers appear more compact and the interface region better conserved when the RNA G4 adopts the dimeric binding mode.