Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes

Different models to treat metal-catalyzed enzyme reactions are investigated. The test case chosen is the recently suggested full catalytic cycle of manganese catalase including eight different steps. This cycle contains O—O and O—H activations, as well as electron transfer steps and redox active reactions, and is therefore believed to be representative of many similar systems. Questions concerning modeling of ligands and the accuracy of the computational model are studied. Imidazole modeling of histidines are compared to ammonia modeling, and formate modeling compared to acetate modeling of glutamates. The basis set size required for the geometry optimization and for the final energy evaluation is also investigated. The adequacy of the model is judged in relation to the inherent accuracy achievable with the hybrid DFT method B3LYP. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1634–1645, 2001