Macrocyclic peptides feature in several therapeutically relevant contexts. To provide a proof-ofprinciple of the application of this method to these challenging systems, we selected a small adhoc set of 6 conformationally restrained peptides which were not included in the main dataset (Figures 9 and 10, Table ): 3 inhibitors of HIV-1 protease (PDB: 1b6j, 1b6p, 4cpw); 3 antibiotics: arylomycin C (PDB: 3s04), darobactin (PDB: 7nrf), and vancomycin (PDB: 1rrv). Due to the high number of torsions present in these compounds, they were docked by disabling the AutoStop and search heuristic, and using 100M evaluations. For the complexes in PDBs 1b6j and 1b6p, the top pose was within 2 Å of the crystallographically determined ligand. For 1b6p, this involved two cyclic systems, a 15-membered ring and a 16-membered ring. Interestingly, in the latter, two of the carbons were not resolved in the crystal structure. While these atoms were excluded from the RMSD calculation, the docking was performed with the goal of assessing the application of this method to help refine incomplete structural data and infer the positions of the unresolved atoms in the macrocycle. The re-docking of the 4cpw complex is the only example of this set in which the top pose did not match the crystal structure. The best pose for the third ranked cluster was accurate to within 1 Å and was scored within 1 kcal/mol of the best cluster, showing that while AutoDock-GPU failed to properly rank the poses, the search algorithm showed to be capable of properly sampling the correct pose. For arylomycin C (PDB: 3s04), darobactin (PDB: 7nrf), and vancomycin (PDB: 1rrv) <2 Å RMSD poses were identified as the top result. These antibiotic peptides represent a series of increasing complexity challenges, with a progressively increasing number of torsions and flexible ring systems from arylomycin (24 torsions, 1 macrocyclic ring), to darobactin (32 torsions, 2 macrocyclic rings), to vancomycin (39 torsions, 3 macrocyclic rings). In both arylomycin and vancomycin, the accuracy of the macrocyclic portion is higher than for the linear chains attached to it, likely due to the more specific and constrained interactions established by the former versus the latter. In particular, for vancomycin the higher accuracy portions of the docked pose are near to the intersections of rings, and in regions with more contact with the protein, compared to distal portions of the molecule.