Next, we optimized the CG model of a pillar [5]arene, for which main results are reported in Figure . Geometrical features of the resulting CG model are exclusively compared to those calculated from AAmapped data, since no manually parametrized CG model was available from the literature for this molecule. The mismatches between CG and AA-mapped geoms distributions were effectively reduced during optimization (Figure , green line). The optimized CG model was further validated in a 200 ns simulation, in which geoms distributions correctly overlapped with those calculated from the AA-mapped trajectory (Figure ). Average Rg and SASA values were also found in good agreement (errors: 1% and 5%). Since the CG model of the pillar [5]arene was prepared according to the MARTINI framework, bonds were rescaled between SC5 and EO beads (i.e. cyclic core to arms junctions) and the average Rg of the AAmapped reference was rescaled accordingly (cf. SI section 2.2), while no transformation was applied to its average SASA value. Therefore, the small discrepancy observed between average SASA of the optimized CG and AA-mapped models is expected and the rescaled, average Rg is a better reference to assess this model's bonded parametrization. BP optimization converged within 230 steps (Table ).