For GNNIS, the molecule-dependent parameters (i.e., atomic partial charges and van der Waals radii) of the GNN were set to the same values as for the classical GB-Neck2 model as described in Ref. . The preoptimized structure was further optimized using the BFGS algorithm with a tolerance of 0.025 eV Å -1 as implemented in the ASE package by combining the forces obtained with GNNIS and a QM calculation with CPCM . The dielectric constant used in the CPCM method was set to the same experimental value as in the GNNIS model (see Ref. for exact values). The free energy of the further optimized structure G( r) was evaluated according to,