We first comment the optimization case of the CG model of β-Cyclodextrin, which main results are reported in Figure . Geometrical features of the resulting CG model are compared to both those calculated from AA-mapped data and from the CG model available from the literature 60 (cf. section 6.2). The mismatches between CG and AA-mapped geoms distributions were effectively reduced during optimization (Figure , green line). However, in the 200 ns validation simulation, geoms distributions of the optimized CG model did not perfectly reproduce those calculated from the AA-mapped trajectory (Figure ). A small issue in the topology of the model, related to the size of CG beads used in the MARTINI framework, prevents proper closing of angles between P4-P2-P2 beads (i.e. maroon-pink-pink and Figure , angle 4) and slightly affects other geoms distributions. These small mismatches in local geometry are acceptable at CG resolution, in the context of this molecular structure. According to the MARTINI framework, fixing them would require modifications such as scaling the bonds lengths between P4-P2 beads (i.e. maroon-pink), which would introduce other forms of error in the CG model, notably related to non-bonded parametrization. Nonetheless, the optimization process yielded appropriate BP in the context of the CG topology provided for β-Cyclodextrin and average Rg and SASA are in very good agreement with the AA-mapped trajectory (i.e. both errors < 1%). BP optimization converged within 206 steps (Table ). We tested the manually parametrized CG model of β-Cyclodextrin in a 200 ns simulation. Swarm-CG scoring function yielded a BP score of 71.9 for this model, indicating larger discrepancies in local geometrical features (Figure ) compared to the optimized CG model which obtained a BP score of 28.2, with respect to the AA-mapped reference trajectory. BP optimization produced marginal improvements on average Rg error (0.2 Å or 3.5 points) for this small and cyclic molecule, with respect to the available manual bonded parametrization (Table ).