To test the performance of the sGADFT approach, we have chosen two reference systems of different size for which the lowest energy structures have previously been determined via a combination of high-resolution conformer-selective IR spectroscopy paired with electrospray ionisation and cryocooled ion traps, supported by a traditional computational approach (as described above) to determine the most stable structures. The first test case system comes from the work of Masson et al. who leveraged ion-mobility techniques to identify and separate two conformational families of the protonated GPGG peptide (Fig. ) with different collisional cross sections, and acquired respective spectroscopic data. Major conformers of each family were determined as involving either the cis or trans isomers of the proline residue. The 3D structure determination was previously estab-lished by running SA ab initio MD starting from random cis/trans structures extracted from the Protein Data Bank (PDB). The search was conducted at the DFT level with the B3LYP functional and a 6-31G basis set, with extensive trials of heating temperatures and annealing rates for total simulation times of several tens to hundreds of picoseconds. After this first exploration, isomers were structurally and energetically selected, and locally relaxed at the B3LYP/6-31G(d,p) level of theory to provide a final set of 13 cis and 29 trans energetically low-lying candidate structures, which serve as reference pool in this work. Comparison of theoretical harmonic vibrational frequencies (at B3LYP/6-311++G(d,p) level) including isotopic substitutions with the measured spectra clearly confirmed that the lowest-energy configuration of each family of these two sets corresponded indeed to the most abundant of the observed conformers. Similarly, in 2010, Nagornova et al. published highlyresolved IR spectra of the doubly protonated gramicidin S peptide (Fig. ) featuring a D rather than a L enantiomer of a phenylalanine. Since the experimental data indicated some symmetry (C2) for the major conformer, a SA exploration of the high-dimensional PES could be performed by imposing structural constraints over multiple FF99SB and FF02polEP 65 force field trajectories. The 3D structure was finally determined by calculating B3LYP/6-31G(d,p) spectra of few candidates.