Recently, an alternative approach to biomolecular force field design has been proposed, named the QUantum mechanical BEspoke (QUBE) force field, in which virtually all force field parameters are derived specifically for the molecule under study directly from a small number of QM calculations. QUBE shares its functional form with the OPLS force field, and so is rapid to evaluate in the context of alchemical free energy calculations. Full details may be found elsewhere. In brief, non-bonded (charge and Lennard-Jones) parameters of the QUBE force field are derived from atoms-in-molecule partitioning of the ground state QM electron density, in particular, employing the Tkatchenko-Scheffler relations for van der Waals interactions. 17 QUBE bond and angle parameters are derived from the QM Hessian matrix, using the modified Seminario method, while anharmonic dihedral parameters are fit to relaxed QM torsion scans. Small molecule QUBE force fields may be derived using the QUBEKit python package, and they have been extensively validated against experimental liquid properties. Atoms-in-molecule protocols are available as part of the ONETEP linear-scaling density functional theory (DFT) software, and hence QUBE non-bonded parameters may be readily derived for entire proteins comprising thousands of atoms. These parameters have been supplemented by compatible libraries of bonded parameters, and simulations of protein dynamics using the resulting QUBE force fields have been validated against experimental NMR observables. To date, the QUBE force field has been used to compute absolute binding free energies of a series of benzene derivatives to the L99A mutant of T4 lysozyme and relative binding free energies of several flexible inhibitors of p38α MAP kinase. In both cases, mean unsigned errors in protein-ligand binding free energies under 1 kcal/mol were reported. Such accuracy was shown to be broadly similar to that of the OPLS-AA force field in these cases. In the initial development of QUBE, the OPLS functional form has been retained for compatibility with existing MM software (for example, these studies used the MCPRO software ).