Reversible dioxygen binding to hemerythrin.

A combination of conventional quantum chemical methods and a recently developed mixed quantum mechanical/molecular mechanical (QM/MM) method (QSite) is used to determine the different energetic components involved in reversible binding of O(2) to hemerythrin. The use of an accurate quantum chemical description of the active site and the inclusion of effects from the surrounding protein environment are both essential to achieve reversibility and thus to model accurately the binding of O(2) to the carboxylate-bridged diiron center in the protein. The major contributions from the protein environment stabilizing dioxygen binding are (1) the van der Waals interaction between the bound dioxygen and the protein atoms and (2) an increase in the hydrogen bonding energy of an imidazole group, ligated to one of the iron atoms, and a neighboring carboxylate side chain in the second coordination sphere. The protein strain energy for this system is negligible. The calculated total O(2) binding free energy is in good agreement with that derived from the experimental equilibrium constant.