Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database

The number of entries in the Protein Data Bank (PDB) has doubled in the last decade, and it has increased tenfold in the last twenty years. The availability of an ever-growing number of structures is having a huge impact on the Structure-Based Drug Discovery (SBDD), allowing investigation of new targets and giving the possibility to have multiple structures of the same macromolecule in a complex with different ligands. Such a large resource often implies the choice of the most suitable complex for molecular docking calculation, and this task is complicated by the plethora of possible posing and scoring function algorithms available, which may influence the quality of the outcomes. Here, we report a large benchmark performed on the PDBbind database containing more than four thousand entries and seventeen popular docking protocols. We found that, even in protein families wherein docking protocols generally showed acceptable results, certain ligand-protein complexes are poorly reproduced in the self-docking procedure. Such a trend in certain protein families is more pronounced, and this underlines the importance in identification of a suitable protein–ligand conformation coupled to a well-performing docking protocol.