Efforts to unravel the principles of enzymatic catalysis have important practical implications. For instance, comprehensive insights into enzyme reaction mechanisms are invaluable in the strategic development of pharmaceuticals. This involves developing inhibitors that imitate the structure of either the intermediate stages or the transition states of enzymatic reactions. Biocatalysis has furthermore been revolutionized by enzyme engineering techniques, and mechanistic information plays a crucial role in guiding that process. While classical molecular dynamics (MD) simulations play a central role in identifying binding sites and key enzyme-substrate interactions, and can inform sitedirected mutagenesis studies designed to optimize enzymatic efficiency, MD force fields cannot provide mechanistic information for enzyme-catalyzed reactions, for which a quantum-chemical approach is required.