Computational enzymology: insight into biological catalysts from modelling

Molecular modelling and simulation can give atomic-level understanding of the fundamental mechanisms of enzyme catalysis. For example, modelling can identify likely enzyme reaction mechanisms, analyse catalytic interactions, and identify determinants of reactivity and specificity. Combined quantum mechanics/molecular mechanics (QM/MM) methods are an important technique in this maturing field of computational enzymology. By coupling quantum chemical ( electronic structure) calculations on the active site with a simpler, empirical 'molecular mechanics' treatment of the rest of the protein, QM/MM methods allow the modelling of reactions in enzymes. In this Highlight, QM/MM techniques are outlined and some recent applications are discussed. These applications illustrate how calculations of this type can be used to interpret and complement experiments, with important potential implications for practical developments such as drug and catalyst design.