Reply to Mouesca et al.: Electronic structure of the proximal [4Fe-3S] cluster of O ₂ -tolerant [NiFe] hydrogenases

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. The critique raised in Mouesca et al. (1) that our cluster model was too small and incorporated spurious constraints is unfounded. In Volbeda et al. (3), only three additional amino acid … [↵][1]2To whom correspondence may be addressed. E-mail: frank.neese{at}cec.mpg.de or wolfgang.lubitz{at}cec.mpg.de. [1]: #xref-corresp-1-1