The average RMSD is relatively large compared to the average RMSD of the M2P2-based EP (3.6 kJ/mol) which can be considered to be very close to an optimal parametrized potential. In a single case, the dimeric CYX tripeptide, the M2P2 potential produced an EP with a relatively high RMSD of 9.0 kJ/mol. The larger error is caused by over-polarization because of close contact between the two CYX tripeptide fragments. By employing a Tholetype damping of the induced dipole-induced dipole interactions, the RMSD was decreased by 2.5 kJ/mol. Damping is part of the Thole-type polarization model in AMOEBA, but it usually is not needed in MFCC-based potentials because the interactions between neighbor- ing polarizable sites are intrinsically included through the fragment calculations from which the parameters are derived. However, when there are close contacts between two fragments that are not covalently bonded (as is the case for the dimeric CYX tripeptide), it may be necessary to include damping. Note that damping has not been used in the CP -based calculations because tests revealed that it only had negligible effects.