Computational enzymatic catalysis – clarifying enzymatic mechanisms with the help of computers

Abstract

Enzymes play a biologically essential role in performing and controlling an important share of the chemical processes occurring in life. However, despite their critical role in nature, attaining a clear understanding of the way an enzyme acts, i.e. its catalytic mechanism, is a cumbersome task that requires the cooperative efforts of a large number of different scientific techniques. Computational methods offer a particularly insightful way to study such mechanisms, always beautifully complementing the information arising from experimental techniques and working as an excellent alternative for assessing the viability of different mechanistic proposals. This review highlights two important computational strategies to study enzymatic catalysis - the cluster modeling approach and the hybrid quantum mechanical/molecular mechanical (QM/MM) method - complemented with a selection of hand-picked examples of our own work.