Importantly, our bespoke parameter derivation methodologies offer the potential for substantial improvements in accuracy. By deriving as many force fields parameters as practical directly from QM, rather than fitting to experiment, the process of force field design becomes an exercise in accurately mapping QM data onto physically-motivated parameters and functional forms. In developing the QUBE non-bonded parameters for proteinligand complexes such as these, only seven parameters have been directly fit to experiment (the van der Waals radii of seven elements), with the remainder being derived from QM.