Figure shows the structures of the systems together with the absolute error in the MFCC-and MFCC(HB)-based electrostatic potentials on the molecular surface defined by twice the vdW radii and the RMSDs evaluated for points on scaled vdW surfaces that thus give the distance dependence of the error. The surface plots reveal that the electrostatic potentials in all four systems display errors of at least 13 kJ/mol in some areas when using the standard MFCC approach. The errors are considerably reduced for MFCC(HB), showing that the lack of hydrogen-bond treatment is a substantial source of error for the standard MFCC approach. Considering the RMSDs evaluated for points on vdW surfaces scaled with different factors, it is clear that MFCC(HB) improves the electrostatic potentials in all cases and at all distances. Focusing on the vdW surface scaled by a factor of 2.0, there is only a modest improvement for the glycine dimer as MFCC(HB) reduces the RMSD by just 14.4% compared to standard MFCC. However, for the other systems, the improvements are substantially more pronounced. The RMSD is lowered by 54.6% for the water decamer, while for the α-helix and β-sheet, it is lowered by 50.7% and 41.9%, respectively. The RMSDs for the vdW surfaces scaled by a factor of 2.0 are also summarized in Table together with RMSDs for the electrostatic potential from multipoles and polarizabilities derived without fragmentation. The latter can be considered the lower bounds when using fragmentation. The RMSDs for the non-fragmented potentials are quite low, ranging from 1.1 kJ/mol for the water decamer, over 1.4 kJ/mol for the glycine dimer, up to 1.8 and 1.9 kJ/mol for the α-helix and β-sheet, respectively. Using standard MFCC triples the RMSDs for the water decamer, α-helix, and β-sheet, increasing the RMSDs by 2.3, 3.7, and 3.5 kJ/mol, respectively, but only 0.6 kJ/mol for the glycine dimer. By instead using MFCC(HB), i.e., preserving the hydrogen bonds in the fragmentation, the RMSDs are increased by just 0.3, 0.5, 0.9, and 1.2 kJ/mol for the glycine dimer, water decamer, α-helix, and β-sheet, respectively. These results demonstrate clearly that MFCC(HB) yields substantially improved multipoles and polarizabilities for larger molecular structures containing hydrogen bonds.