While the previous analyses assessed the quality of the structural as well as energetic predictions of the different surrogate methods, their overall computational cost also plays a major role in the choice of the most appropriate fitness function. To give an overview of the different time scales involved we give estimates of the average time needed for a local geometry optimization for each surrogate method in Table . For the sake of comparison, running a GA search with the B3LYP/6-31G(d,p) reference would take more than 2.5 months on a desktop workstation for the 39-atom GPGG molecule, highlighting the need for more expedient approaches. Although it is found that resorting to a smaller basis set provides the best accuracy, a GPUaccelerated implementation only reduces the elapsed time to the order of a month, while other surrogates bring it down to less than a day for semiempirical methods (PM6, PM7, DFTB3) and only few minutes for force fields (GAFF, AMOEBA).