We first comment the optimization case of the CG model of a spermine-functionalized dendron reported in Figure , as an example of flexible, branched and directional molecule. Geometrical features of the resulting CG model are exclusively compared to those calculated from AA-mapped data, since no manually parametrized CG model was available from the literature for this molecule. As depicted by the decreasing scores attributed to candidate sets of BP during optimization (Figure , green line), the process effectively minimizes mismatches between CG and AA-mapped geoms distributions, which were reduced by a factor of 2 when comparing the initial set of BP (step 1) to those of the optimized model (step 249). BP optimization converged within 255 steps (Table ). The optimized CG model was further validated in a 200 ns simulation. Distributions of the bonds and angles correctly overlap between the optimized CG and AA-mapped models (Figure ) and, on a larger scale, average Rg and SASA values are also in very good agreement (i.e. both errors < 3%). Average SASA of the optimized CG model is slightly increased with respect to that of the AA-mapped, which is due to the scaling of bonds lengths between CG beads of the aromatic ring and is inherent to the MARTINI framework (cf. SI section 2.2). This scaling has little incidence on Rg values in this model and the AA-mapped average Rg was calculated without considering any offset.