Theoretical Studies of the Bonding of O₂ to Hemoglobin; Implications for Cooperativity

Abstract

We examine the molecular description of bonding of O₂ to hemoglobin (Hb) and myoglobin (Mb) using the results of ab initio calculations on models of the active site. We find that the ground state of deoxyMb is high spin (denoted as q) with the Fe 0.28Å out of the Ν plane. The origin of this out-of-plane displacement is found to be nonbonded repulsions between the axial ligand and the porphyrin Ν orbitals. An excited state with intermediate spin (denoted as t) is 17 kcal higher in energy with the Fe only slightly out of plane. Bonding of O₂ to Mb_q leads first to a spin triplet intermediate (Mb_q)(O₂) followed by spin inversion to a spin singlet (Mb_t)(O₂) in which the Fe has the electronic configuration of the intermediate spin state. Available experimental evidence is consistent with these results. The theoretical potential curves are used to examine the Perutz-Hopfield explanation of the cooperative bonding of O₂ to Hb. Our model suggests an alternative electronic origin of cooperativity that would not require the large differential protein forces characteristic of the Perutz-Hopfield model.

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