The poor correlation between Drude and XDM dispersion coefficients is exacerbated by five atom types where the force-field dispersion coefficient is several times larger than the corresponding XDM value (Table ). Atypically large Lennard-Jones parameters have been assigned to these atoms. For example, atom type ND2R5D, which represents the nitrogen at the 9 position of purines, has an parameter of -0.23 kcal/mol, which is a factor of 2 larger than is typical for nitrogen atom types. The procedure that determined these parameters included unconventional target data, such as QM interaction energies and lattice energies. These terms are less sensitive to the Lennard-Jones parameters than traditional parameterization target data, like the density or enthalpy of vaporization, so it is possible that the parameters were over-fit. Imposing constraints on the Lennard-Jones parameters to ensure that the C 6 coefficients are in the typical range for each element would be a simple way of avoiding parameters that cause the long-range dispersion interactions to become unrealistically large.