It may be possible to address this issue by changing the functional form of the torsional component of the force field. The functional form currently used is inaccurate due to the parameter dependency on only a single dihedral angle. The coupling between torsional terms has been addressed in a number of different ways. These include the use of the CMAP term in CHARMM22, a grid based correction used to improve the backbone torsional energetics. Extending the CMAP correction so it is dependent on the χ 1 sidechain dihedral angle has also recently been investigated. The functional form could also be improved by adding a torsion-torsion coupling term as employed in previous studies. Importantly, the flexibility of the QUBE parametrization process means that changes to the torsional parameters are not the only alterations that could be made to improve the accuracy of the benchmark validation tests studied here. It is not just protein-protein interactions that determine structure, but also interactions with the water model. In particular, the balance between electrostatic and dispersive interactions has been shown to be crucial. Interactions between the QUBE force field and the TIP3P water model may be responsible for some of the instabilities in structure that we have observed, and development of a QUBE water model may lead to improved dynamics and computed free energies of hydration. An advantage of using a parametrization scheme that depends almost entirely on QM data is that alterations to the parametrization strategy or functional form can be readily inserted into the existing workflow. There is future scope for improvement in the choice of exchange-correlation functional used to derive non-bonded parameters, for example through the use of hybrid functionals, or the choice of electron density partitioning methods, 66 or the addition of off-center charges to model electron anisotropy effects. More fundamentally, we have the opportunity to investigate improvements to the functional form of the force field itself, for example, by adding higher order dispersion terms beyond the dipole-dipole interaction or by altering the short-range repulsion term. A future QUBE polarizable force field is also envisaged and, towards this goal, the derivation of accurate atoms-in-molecule atomic polarizabilities is under investigation. As presented in the Results section, the general picture that emerges is that this first generation quantum mechanical bespoke force field is an improvement over legacy OPLS-AA and OPLS-AA/L force fields, but is out-performed by the most recent OPLS-AA/M force field for simulated dynamics of folded proteins in their native state. While we have previously shown that DDEC charges are not too dependent on small conformation changes, 28 further investigation is needed to establish the utility of QUBE for protein folding simulations.