ciple the overall diversity of the LM (cf. Section 4.2.2) but becomes essential to explore the very low energy regions of more complex systems. Indeed, for gramicidin, the greater number of low-energy minima was obtained by the elitism fraction capable of identifying the putative GM (Fig. and). Therefore, mitigating elitism with other mutation-like operators could potentially improve the search power in the low-energy regime by providing a certain diversity of structures visited while maintaining low energies. B3LYP/6-31G(d,p) re-optimizations of gramicidin candidates are much more CPU intense than those of the smaller GPGG peptides, so that only structures sampled with 10% elitism and located within 5 kcal/mol could be retained for subsequent optimizations. It is therefore crucial that the surrogate, although not optimal, provides relevant candidates located in a range of only a few kcal/mol, as the number of structures and their refinement cost increases considerably with the size of the system. Again, we plot relative energies and RMSDs against DFT re-optimized geometries in Figure , and report averages in Table . For gramicidin, AMOEBA performs as well as for GPGG with a MAE around 4 kcal/mol and small 0.3 Å average backbone RMSD. Successfully, the three lowest candidate structures relax to the DFT GM (Fig. ). For GAFF, the geometries of the candidate structures are also very similar to their closest DFT minima, but relative energies are significantly off due to GAFF's inability to correctly reproduce the lower regions of the DFT PES of this system. By visualizing the LM in the RG-NH space in Figure , we notice that GAFF biases the search towards higher-energy DFT regions. In these, GAFF does rather well on relative energies despite a large energy offset (∼18 kcal/mol, Fig. ). Hence, we conclude that GAFF cannot reliably approximate the energetics for screening low-energy gramicidin structures and sample realistic regions of the PES, which the polarizable AMOEBA force field, on the other hand, seems to achieve surprisingly well.