The Art and Science of Molecular Docking

Molecular docking has become an essential part of a structural biologist's and medicinal chemist's toolkits. Given a chemical compound and the three-dimensional structure of a molecular target—for example, a protein—docking methods fit the compound into the target, predicting the compound's bound structure and binding energy. Docking can be used to discover novel ligands for a target by screening large virtual compound libraries. Docking can also provide a useful starting point for structure-based ligand optimization or for investigating a ligand's mechanism of action. Advances in computational methods, including both physics-based and machine learning approaches, as well as in complementary experimental techniques, are making docking an even more powerful tool. We review how docking works and how it can drive drug discovery and biological research. We also describe its current limitations and ongoing efforts to overcome them.