In the following, we examine the impact of MFCC(HB) compared to standard MFCC for realistically sized systems by evaluating the embedding potential, i.e., the electrostatic potential of the entire environment, on the vdW surface of the central quantum subsystem. This is performed for the following molecules in aqueous solution: acrolein, pyridinium, 4nitroanilinium, 4-nitrophenolate, and permanganate, and for the following moieties in protein environments: PRSB + in C1C2 and HBDI -in GFP. The surface plots in Figure show MFCC(HB)-based embedding potential and the difference between standard MFCC-and MFCC(HB)-based embedding potentials. Here it can be seen that there are substantial differences between the standard MFCC-and MFCC(HB)-based embedding potentials for all the systems. Indeed, the differences are at least ±26 kJ/mol in some areas of the vdW surface of the solute-solvent and PRSB + in C1C2 systems and at least ±79 kJ/mol for HBDI -in GFP. The largest differences tend to be in areas where the value of the embedding potential is high. Here it is worth noting that the differences are roughly an order of magnitude smaller than the absolute MFCC(HB)-based embedding potential. The RMSDs considering the entire vdW surfaces are presented in Table . There appears to be some correlation between the charge of the quantum subsystem and the size of the RMSD. The highest RMSDs are associated with systems containing a negatively charged quantum subsystem, i.e., 4-nitrophenolate in water, permanganate in water, and HBDI -in GFP that have RMSDs of 40.2, 63.6, and 57.9 kJ/mol, respectively. Conversely, lower RMSDs are found for the systems with a positively charged quantum subsystem, i.e., pyridinium in water, 4-nitroanilinium in water, and PRSB + in C1C2 where the RMSDs are 17.5, 14.1, and 27.2 kJ/mol, respectively.