Given the expected benefits of DDEC6 in larger, more flexible molecules, we retain this method as our standard approach, but do investigate both DDEC3 and MBIS further in what follows. It is gratifying that a range of AIM methods have been shown to be promising for flexible force field design, and are available through our QUBEKit interface with QCEngine. Lennard-Jones Parameters As discussed in the Methods section, the default QUBE protocol for deriving the attractive part of the Lennard-Jones potential (B ij in eq 4) from QM tends to lead to dispersion coefficients that are lower than those used in common effective force fields and energy well depths that are constant across atoms of the same element. Model 4b in Table investigates the effects of relaxing this protocol, by introducing two new global, variable parameters (α and β) into the fit, thus moving away from the default Tkatchenko-Scheffler (TS) approach. As expected, a reduction in training set errors is achieved, relative to the default model 0, with these extra fitting parameters. Table shows that this is achieved with α > 1 and β > 0, both factors that act to increase the well depth for atoms with more diffuse electron density (eq 12). Figure plots the dispersion coefficients (summed over all atoms in the molecule) for all molecules in the larger test set, using the identical Lennard-Jones scheme (from model 5b, see later), against the corresponding quantities extracted from the Parsley force field. Unlike previous protocols (see our previous work, 40 and Section S5.2), there is a very good correlation between the two force fields, albeit with a consistent offset.