Relative training set accuracy is retained in the test set To test the accuracy of the designed force fields on molecules outside the training set, we ran simulations of the condensed phase properties of a separate test set of 51 molecules containing H, C, N and O atoms only. The force fields brought through for study were models 0, 1a, 5b and 5d. The first two were chosen as our simplest (but also amongst the least accurate) protocols, differing only by the choice of underlying QM method. In both cases, we see a drop in overall accuracy, compared to the training set, which is to be expected for the larger, more complex molecules found in the test set (Figure ). Again, we do not observe a strong dependence of the results on the choice of QM method, and so the computationally less expensive model 1a, based on the B3LYP-D3(BJ)/DZVP method, should make a good compromise force field. For comparison, we have also run the test set using the Open Force Field Parsley force field 11 using identical protocols. The accuracy in the simulated densities (0.038 g/cm ) is similar to our first two protocols, and the error in the heat of vaporisation (1.18 kcal/mol) is slightly lower. The Parsley force field is based around the AM1-BCC charge scheme, with Lennard-Jones parameters largely retained from the SMIRNOFF99Frosst force field. Thus, there is scope for further refinement of the Lennard-Jones parameters within the current functional form, albeit with many more adjustable parameters than we use here (the five R f ree i parameters in Table ). It is difficult to pinpoint reasons for improvement in accuracy, since the physical properties are derived from many competing effects. However, Figure shows some of the force field parameters for molecules that show differences in performance between our best model (5b), and Parsley. ∆H parsley vap = 8.7 kcal/mol). There are some small differences in charges on the terminal methyl hydrogen atoms, which add up to a large difference in charge on the carbon atoms, but this does not seem to significantly affect the liquid properties. We can compare the accuracy of the protocols developed here with other force fields tested on the same or similar test sets. Using the RESP2 charge assignment method, which is based on fitting to the QM electrostatic potential in implicit solvent, with optimised Lennard-0.024 g/cm 3 and 1.67 kcal/mol. Thus, substantial improvement in energetics is obtained in the current study, at the expense of a slight degradation in liquid density prediction. In that study, only a subset of ten Lennard-Jones parameters (the well depth and radius for each of C, O, N, H and polar H) were optimised for efficiency, though this is still more parameters than our most complex protocol (model 5b has seven adjustable parameters).