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Hemoglobin mediated transport of dioxygen (O2) critically depends on the stability of the reduced... more Hemoglobin mediated transport of dioxygen (O2) critically depends on the stability of the reduced (Fe2+) form of the Heme cofactors. Some protein mutations stabilize oxidized (Fe3+) state (Methemoglobin, Hb M) causing methemoglobinemia and can be lethal above 30 %. Majority of the analyses of factors influencing Hb oxidation are retrospective and give insights only for inner sphere mutations of Heme (His58, His87). Herein, we report the first all atom MD simulations on redox states and calculations of the Marcus ET parameters for the α-chain Hb oxidation and reduction rates for Hb M. The Hb (wild type), and most of the studied α-chain variants maintain globin structure except the Hb M Iwate (H87Y). Using linear response approximation we calculated average energy gaps (), total (λ), protein (λprot), solvent (λsolv) reorganization energies, and redox potentials (E°), and oxidation free energies (ΔG°). The total λ ranges from 0.685 – 0.730 eV in agreement with literature on Hb and simi...
Hemoglobin mediated transport of dioxygen (O2) critically depends on the stability of the reduced... more Hemoglobin mediated transport of dioxygen (O2) critically depends on the stability of the reduced (Fe2+) form of the Heme cofactors. Some protein mutations stabilize oxidized (Fe3+) state (Methemoglobin, Hb M) causing methemoglobinemia and can be lethal above 30 %. Majority of the analyses of factors influencing Hb oxidation are retrospective and give insights only for inner sphere mutations of Heme (His58, His87). Herein, we report the first all atom MD simulations on redox states and calculations of the Marcus ET parameters for the α-chain Hb oxidation and reduction rates for Hb M. The Hb (wild type), and most of the studied α-chain variants maintain globin structure except the Hb M Iwate (H87Y). Using linear response approximation we calculated average energy gaps (), total (λ), protein (λprot), solvent (λsolv) reorganization energies, and redox potentials (E°), and oxidation free energies (ΔG°). The total λ ranges from 0.685 – 0.730 eV in agreement with literature on Hb and simi...