Abstract
Mouesca et al. (1) criticize our analysis (2) of the superoxidized proximal [4Fe-3S]5+ cluster in O2-tolerant hydrogenases (A) that was also studied in Volbeda et al. (3), albeit from a different organism. Both analyses were based on broken-symmetry (BS) density functional theory (DFT) calculations (2, 3), which presently is the only feasible alternative for the treatment of complex systems like A. However, BS-DFT is a crude approach and we regard the differences in refs. 2 and 3 as subtle rather than major.