Second, for proteins we have extended the Molecular Fractionation with Conjugate Caps (MFCC) method to consistently include two-body contributions . While our MFCC-MBE(2) scheme can be considered as a special case of more general schemes for energybased many-body expansions with overlapping fragments , it provided a simple and consistent approach for the quantum-chemical calculation of the energy of proteins and of protein-ligand interaction energies . The MFCC and MFCC-MBE(2) schemes are particularly attractive as starting point for the parametrization of machine-learning potentials because they use single amino acids as fragments . However, our tests showed that while the inclusion of two-body contributions in the MFCC-MBE(2) scheme dramatically reduced the error in protein energies and proteinligand interaction energies compared to the MFCC scheme, the remaining errors can still be substantial.