To investigate the reason for the extreme discrepancies between calculations at different dielectric constants residue-wise energetic contributions to ligand binding are investigated using the free energy decomposition scheme of g mmpbsa. For visualization the energies given as kJ per mole are mapped onto the structure (see Figure and S1). The energetic contributions per residue along the protein sequence between a dielectric constant of 2 and 8 (shown in Figure ) highlights extreme discrepancies for CDB, whereas only the CDB pattern with =8 agrees with the patterns for DB, DDB and HDB, which are very similar. Therefore, calculations performed with a dielectric constant of 2 are considered as untrustworthy and protein residues with most important energetic contributions are compared between the DB and its metabolites at =8 (see Figure ). The contributions appear to be highly similar, except for Lys483, which shows increased variations and tends to more favorable energies for DB than its metabolites.