Also, RNase H crystal structures have suggested that the cation occupying the A site has a perfect octahedral hydration shell, while site B coordination is initially frustrated, with a distorted hydration geometry. Release of this frustration was thought to play a key role in catalysis. The available crystal structure of M5 N-terminal domain 10 paints a very different picture, with a perfect octahedral coordination for site B Mg 2+ and a distorted square-planar coordination in site A. Note that this square planar coordination may be due to limited resolution of structures, difficulty to identify, and that in our molecular simulations both cations have a octahedral hydration shell, with 6 ligands coordinated. Since a thermodynamically favorable reaction pathway, with a low free-energy barrier could still be found in simulations, release of an initial geometric frustration does not seem to be an essential feature for these reactions.