where = 1.0 kcal/mol is a scaling factor, and QM ( ) and MM ( ) represent the relative energies of conformations compared to the QM and MM global minima, respectively. A weight factor ( ) controls the contribution of each grid point to the objective function. It is constant up to a first cutoff (1.0 kcal/mol) and then attenuates to the second hard cutoff (10.0 kcal/mol) after which all weights are zero: