We first analyze the energetics, computing the rela-tive energies of the three protein configurations (Figure ). The semi-local PBE functional without longrange vdW interactions predicts a lower energy for the transition state than the folded state. In contrast, both MBD@rsSCS and FCO-MBD predict the folded state as the lowest-energy structure, highlighting the crucial stabilization provided by vdW dispersion. Notably, the FCO-MBD method, shown to give reliable prediction of dispersion energy for S12L systems in Figure , predicts a stabilization of 125 kcal/mol for the folded structure, driven by vdW forces. While these calculations neglect the influence of water and ions in physiological conditions, they still offer insight into the critical role of vdW dispersion in protein folding, in line with earlier findings . Next, we examine the NCI isosurfaces (Figure ). The general trends are consistent with those observed for S12L and L7+ molecules: the inclusion of MBD polarization density leads to smoother, more connected NCI isosurfaces, quantified by a volume enhancement factor γ ≈ 2.5. To illustrate this, we zoom into the regions around selected residues (TRP8, ARG17, TYR20) of Fip35-WW. Using semi-local density, the NCI isosurfaces FIG. : NCI isosurfaces (s = 0.5) of Fip35-WW protein in the folded state computed using PBE and PBE+MBD density. Regions of the protein structure with the largest differences are highlighted in ellipsoids, with the vicinity of TYR20 and ARG17 residues additionally displayed in magnification. The right panel shows the view on Fip35-WW from the direction of TRP8 residue (in brown), as indicated by side eye pictogram. For reference, ARG17 and TYR20 residues shown in the central panel are colored in pink and purple, respectively. The images are created in the ChimeraX software using the density gradients calculated with the NCImilano program .