First, quantum-chemical methods provide a non-empirical approach which can potentially provide highly accurate interaction energies. Therefore, they can be used to guide the development of empirical energy functions, to validate their accuracy, and to identify their shortcomings (e.g., for partially covalent interactions ). Second, they can be applied for non-standard ligands that contain atoms or structural motifs that are not adequately covered by classical force fields. An important example are metal-based drugs, which are of particular interest as novel anti-infectives (for an example, see Ref. ), but are not routinely amenable to classical docking methods . Third, quantum-chemical calculations can serve as the basis of accurate machine-learning potentials , which can greatly boost their applicability to large biomolecular systems.