Numerous multi-scaling methods have also been developed to combine FG and CG representations within the same calculation, with the goal of striking a favorable balance between the higher accuracy of the FG resolution and the higher efficiency of the CG resolution. Among these, mixed-or adaptive-resolution approaches are based on FG and CG regions coexisting spatially in the same system. Considering a single solute in a given solvent (e.g. hydrated macromolecule or lipid bilayer), a particularly interesting combination of this type relies on embedding the FG solute in a FG solvent region itself surrounded by a CG solvent region, the two regions being separated by a buffer layer permitting FG↔CG mixing or interconversion. On the one hand, this combination provides a much more accurate FG treatment of short-range solvation compared to a direct solvation of the FG solute in the CG solvent . On the other hand, it is expected to retain most of the efficiency gain associated with a CG resolution of the solvent considering that solvent-solvent interactions in the bulk are typically determinant in terms of computational costs. Another key advantage of this setup is that it only requires the design of a CG model for the solvent, which is generally much easier than the corresponding task for the solute.