Microscopic model of carbon monoxide binding to myoglobin

We present a microscopic model of carbon monoxide (CO) binding to myoglobin which reproduces the experimentally observed Arrhenius pre-exponential fac tor of 10(9) s(-1) and activation enthalpy distribution centered at 12 kJ/m ol. The model is based on extensive ab initio calculations of CO interactin g with a model heme-imidazole group which we performed using a fully quantu m mechanical Hartree-Fock/density functional theory (HF/DFT) hybrid method. We fit the HF/DFT calculated energies, obtained for over 1000 heme-CO stru ctures with varied CO and iron positions and orientations for both high (S= 2) and low (S=0) spin states, to a model potential function which includes a bonding interaction in both of the spin states, electrostatic, and anisot ropic Lennard-Jones-type interactions. By combining the x-ray determined pr otein structure with this potential and protein-CO interactions and interna l heme interaction potentials obtained from established molecular dynamics literature, we calculate the energy required for the CO to reach the spin c rossing from the heme pocket. We find that the transition between the two s pin states occurs when CO and iron have activation enthalpies of 8 kJ/mol a nd 3 kJ/mol, respectively, which are necessary to move CO towards the iron and the iron atom relative to the heme plane N-pyr. At the same time we fin d that 1 kJ/mol is needed to move N-epsilon of His-64 and C-gamma of Val-68 relative to the heme group. The requirement that these motions be synchron ized reduces the Arrhenius pre-exponential by a factor of 150 from the 10(1 2) s(-1) obtained from CO motion across the heme pocket, leaving a factor o f similar to 6 to account for CO orientation and nonadiabaticity of the ele ctronic spin change. The observed width of the enthalpy distribution is rep roduced by assuming a Gaussian distribution of the heme positions with a st andard deviation of 0.2 Angstrom. We characterize the conformational relaxa tion by calculating an enthalpy barrier using x-ray structures of myoglobin in both the MbCO photoproduct and deoxy conformations, and we find a small difference, similar to 5 kJ/mol, between the two conformations. (C) 2000 A merican Institute of Physics. [S0021-9606(00)01239-3].