Outstanding challenges in protein–ligand docking and structure‐based virtual screening

With an ever‐increasing number of protein structures being solved by X‐ray crystallography, the use of protein–ligand docking algorithms to assess candidate ligands for a binding site has become commonplace. In particular, over the last decade, high‐throughput docking has been widely applied to the virtual screening of large chemical databases for supporting hit‐finding programs in drug discovery. However, the techniques and practice of protein–ligand docking in general, and of structure‐based virtual screening in particular, are still evolving and significant limitations remain to be addressed. In this review, we seek to highlight some of the active areas of research and debate in this promising, but challenging, field.