Proteome-scale docking: myth and reality

Docking is the computational method of choice to quickly predict how a low molecular-weight ligand binds to its macromolecular target. Despite persistent problems in predicting binding free energies, docking has undergone significant advances in numerous topics (throughput, target flexibility). The ever increasing availability of high-resolution X-ray structures and the development of more reliable comparative models for proteins of pharmacological interest paved the way to apply protein–ligand docking to multiple targets to predict main and off-targets for bioactive compounds and even to repurpose existing drugs. Applying docking to multiple targets brings an additional level of complexity in scoring numerous and heterogeneous docking poses. Despite undeniable successes, proteomewide docking should, however, be considered with caution with regard to recall and precision of the predictions.