It is well-known that the degree of flexibility of the ligands has a direct impact on the docking performance. The DockThor program was originally developed to deal with highly flexible compounds, including peptides . The DockThor program performed well for the protein-ligand complexes with up to 14 rotatable bonds, comprising a great diversity of flexible compounds, achieving mean success rates of 70%, 78% and 92% for the top-1, top-2 and lowest-RMSD poses, respectively. Despite solving some important issues, the initial automatic preparation of the structures performed by PDBbind did not provide an optimised hydrogen bond network and appropriate assignment of protonation/tautomeric states of the complexes. The preparation of the structures using PROPKA and Epik generated an optimized orientation of the hydrogen atoms and suitable protonation/tautomeric states of the ionizable groups from both protein and ligand. These changes are particularly important for docking programs that explicitly consider hydrogen atoms and use scoring functions based on force fields. In such cases, the wrong orientation of hydrogen atoms can lead to extremely high van der Waals energies, underestimation of hydrogen bond interactions, and incorrect electrostatic repulsions between charged groups.