First, we investigate the use of two relatively high level QM methods. The ωB97X-D/6-311++G(d,p) method is used for bonded parameter derivation in earlier QUBE force fields, as well as the OPLS-AA/M protein force field. The B3LYP-D3(BJ)/DZVP method is used for bonded parameter fitting in the Parsley force field and has been shown to give a good compromise between accuracy and computational expense for gas phase conformational energetics of small organic molecules. It has been shown that the choice of DFT functional is not too critical in the reproduction of molecular electrostatic potentials, while larger basis sets afford some improvements in accuracy. However, relatively little is known about how this choice translates to force field accuracy. Runs 0 and 1a reveal that this choice is not critical, with nearly identical training set accuracy obtained for both liquid densities (0.027 g/cm 3 ) and heats of vaporisation (0.77 vs 0.73 kcal/mol). It should be emphasised that this does not mean that the non-bonded parameters themselves are identical. Table shows the final R f ree i parameters after ForceBalance training. There is a notable reduction in the radius of the N atom, using the B3LYP-D3(BJ)/DZVP method, and corresponding increase in both the polar and non-polar H atoms. This backs up the recent assertion that improving the accuracy of atomic charges is unlikely to improve calculation accuracy without a corresponding optimisation of Lennard-Jones parameters. For comparison, in run 1b, we employed the HF/6-31G(d) method, which has been used historically for the fitting of force field ESP charges. The argument goes that this method produces a fortuitous over-polarisation of the electron density in the gas phase to yield charges that are suitable for condensed phase modelling, and so we perform these electron density calculations in vacuum (Table ). The results are very similar to the two higher level QM methods in implicit solvent, but perhaps this is not too surprising, given the success of many force fields that are built from the HF/6-31G(d) method. However, as we will show,