A quantum chemical approach for the mechanisms of redox-active metalloenzymes

During the past 20 years, quantum chemistry has grown to be a significant part in the investigation of mechanisms for redox-active enzymes. In our group we have developed an approach that has been applied to a large number of such systems. Hybrid density functional theory (hybrid DFT) has from the start of these investigations been the leading electronic structure tool. An understanding of how the method works in practice has significantly improved the accuracy and applicability. During the past ten years, it has been found that the results for redox enzymes mainly depend on the chosen fraction of exact exchange in the functional, and that a choice of 15% has worked best. The idea has therefore been to vary that fraction over a reasonable range and study the relative energy dependence. For modeling the enzymes, a cluster approach has been developed. In the present review the development of the method we used is described from its start in work on photosystem II, fifteen years ago. Examples from a few recent applications are described, where the metals have been iron, nickel, copper, cobalt or manganese. The results are in excellent agreement with available experiments, and a large number of new predictions have been made.