The multi-copper oxidases (MCO) couple four one-electron oxidations of substrates at the mononuclear type 1 copper (Cu-T1) site with the four-electron reduction of dioxygen at the trinuclear copper cluster (TNC). By correlating experimental and theoretical data, an unambiguous mapping between the structural, energetic and spectroscopic properties of the various intermediates in the MCO reaction cycle can be established. In terms of theory, these studies involved quantum mechanics (QM; density-functional theory and multi-reference self-consistent field) calculations,[1,2] combined QM and molecular mechanics (QM/MM) modelling, ranging from standard QM/MM optimisations [3,4,5] to the combination of QM/MM optimisation with EXAFS spectroscopy [6] and QM/MM free-energy perturbations.[7,8] Combination of these approaches enabled to address various spectroscopic, thermodynamic and kinetic properties of MCOs. In this talk, it will be demonstrated that the MCOs are not only an attractive playground for theoretical methods, but the results of the calculations (when carefully correlated with and benchmarked against experimental data) can also be used to draw unambiguous conclusions about MCO structure and reactivity. [1] Chalupský, J.; Neese, F; Solomon, E. I.; Ryde, U.; Rulíšek, L. Inorg. Chem. 2006, 45, 11051. [2] Vancoillie, S.; et al. J. Phys. Chem. B 2010, 114, 7692. [3] Rulíšek, L.; Solomon, E. I.; Ryde, U. Inorg. Chem. 2005, 44, 5612. [4] Shleev, S. et al. Electroanalysis 2012, 24, 1524. [5] Srnec, M.; Ryde, U.; Rulíšek, L.: Faraday Discuss. 2011, 148, 41. [6] Ryde, U.; Hsiao, Y.-W.; Rulíšek, L., Solomon, E. I.: J. Am. Chem. Soc. 2007, 129, 726. [7] Hu, L.-H. et al. J. Phys. Chem. B 2011, 115, 13111. [8] Li, J.-L.; Farrokhnia, M.; Rulíšek, L.; Ryde, U. J. Phys. Chem. B 2015, 119, 8268.

Catalytic cycle of multi-copper oxidases studied by theoretical methods

251st National Meeting (2016)

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