Unmasking catalytic reaction mechanisms: From small molecules to enzymes

In 1998 John Pople and Walter Kohn shared the Nobel Prize in Chemistry for the development of wave-function theory (WFT) and density-functional theory (DFT) methods, respectively. In 2013 the Chemistry Nobel Prize was awarded to Martin Karplus, Michael Levitt, and Arieh Warshel for the development of multi-scale methods. These electronic structure methods cover a wide range of accuracy and applicability. WFT methods are very accurate and are applicable to small systems (containing dozens of atoms), DFT methods are less accurate and are applicable to larger systems (containing hundreds of atoms), whilst multi-scale methods are the least accurate and are applicable to very large systems such as proteins and enzymes. In this computational chemistry journey we use this entire range of electronic structure methods to explore catalytic mechanisms in a variety of systems, ranging from small molecules to enzymes. We use WFT methods to investigate interand intra-molecular proton transfer reactions catalyzed by inorganic acids[1,2,3,4] and to computationally design potent antioxidants.[5,6] We use DFT to explore the inversion reactions of corannulene and sumanene on graphene nano-flakes,[7] and we use multi-scale methods to decipher the catalytic mechanism of cholesterol oxidase.[8,9]