or OpenMM. Of these conformers, the lowest energy result is taken to the QM optimisation stage. The QM structural optimisation is performed using either PSI4 or Gaussian, both run through QCEngine 54 with an ultra-fine grid. If the first, lowest energy conformer fails to optimise after 50 iterations, the next conformer is passed instead. The QM optimised coordinates are used as input for an electron density calculation, a Hessian matrix calculation and optional 1D torsiondrive calculation(s) (Figure (a)). The Hessian matrix is used to calculate all bond and angle parameters (k r , r 0 , k θ , θ 0 ) via the modified Seminario method. QUBE uses atoms-in-molecule (AIM) electron density partitioning to obtain all nonbonded parameters of the force field. AIM methods partition the total electron density n(r) into overlapping atomic densities n i (r) according to: