Search

In heme-containing proteins the heme group is usually non-covalently bound in a pocket. Molecular dynamics (MD) simulations have been performed to estimate the barrier height for heme–protein separation. In simulations of myoglobin dissolved in water, a force has been applied to pull the heme out of the binding pocket. With forces above 0.5 nN, the heme group is easily pulled out of the pocket in times of the order of tens of picoseconds. With weaker forces, heme release becomes too slow to be monitored in an MD simulation covering a couple of hundred picoseconds. These results are consistent with a free energy barrier to heme release of about 100 kJ/mol. The results show that the main energetic change that occurs during the release is a conversion of heme/protein Lennard–Jones energy into heme/water Lennard–Jones energy. The release is essentially barrierless in energy indicating that the main part of the barrier is entropic.

The temperature dependence of the coordination of CO to two hemoproteins, myoglobin (Mb) and leghemoglobin (LegHb), has been studied by absorption spectroscopy. All spectral changes in the electronic and infrared ranges are fully reversible between 8 and 88°C and indicate a more linear orientation of the distal ligand with increasing temperature. The characteristic energy for the above spectral changes is around 200 cm −1 or identical to the Fe-Imidazole (Im) mode in hemoproteins. Our results are also compared with recent models for the dynamics of CO adsorbed at the surfaces of transition metals. Based on these surface models we suggest that our observed temperature dependences stem from thermal excitations of the Fe-Im vibration. This implies a so far undocumented mechanism by which the Fe-proximal bond influences the binding and energy dissipation at the active site of hemoproteins.