The collection of thousands of structures provided by the GA is followed by their ultimate re-optimization at the reference level. For this purpose, only surrogate structures within 10 kcal/mol of their putative GM are selected and locally relaxed with DFT (B3LYP/6-31G(d,p)). To establish the actual accuracy of the surrogate, Figure compares the energies and coordinates between the AMOEBA LM and their re-optimized counterparts and Table reports respective MAE on energy and bb-RMSD for all schemes. As expected, relative energies are not perfectly reproduced and largest errors (outliers) cannot be systematically attributed to larger RMSDs. However, AMOEBA provides a rather good MAE of only 1.9 kcal/mol for the cis isomers, while it increases to 4.4 kcal/mol for the trans structures. Surprisingly, the relative energies obtained for the GAFF (fixed point charge) force field are only slightly worse than the ones Table : GPGG: MAE(∆ Ẽ) a in [kcal/mol] and average backbone RMSD in [ Å] between the surrogate LM and their re-optimized counterparts at B3LYP/6-31G(d,p). NLM is the number of LM re-optimized within 10 kcal/mol from the putative GM. Surrogate/isomer MAE(∆ Ẽ) Avg bb-RMSD NLM AMOEBA/cis 1.9 ± 1.5 0.28 ± 0.10 31 GAFF/cis 2.9 ± 1.9 0.29 ± 0.14 94 AMOEBA/trans 4.4 ± 2.9 0.31 ± 0.21 64 GAFF/trans 4.0 ± 2.5 0.38 ± 0.23 87 a as defined in Table .