Protein–ligand docking: Current status and future challenges

Understanding the ruling principles whereby protein receptors recognize, interact, and associate with molecular substrates and inhibitors is of paramount importance in drug discovery efforts. Protein-ligand docking aims to predict and rank the structure(s) arising from the association between a given ligand and a target protein of known 3D structure. Despite the breathtaking advances in the field over the last decades and the widespread application of docking methods, several downsides still exist. In particular, protein flexibility-a critical aspect for a thorough understanding of the principles that guide ligand binding in proteins-is a major hurdle in current protein-ligand docking efforts that needs to be…