DYNAMICS OF LIGAND-BINDING TO HEME-PROTEINS

The dynamics of CO or O2 binding to myoglobin are examined theoretically with particular emphasis on the effect of the globin on the barriers along possible reaction paths. By use of a diabatic representation, in which a model ligand moves in the potential of a rigid protein, two paths in or out of the heme pocket are found in myoglobin; one is by the E helix near the distal histidine and the other near the intersection of the B, D and E helices. Classical trajectories calculated for a photo-dissociated ligand in the diabatic approximation yield complicated motion; the ligand tends to spend considerable time undergoing multiple collisions with the protein matrix in the wells between barriers. To investigate the height of the barriers, the adiabatic limit is used; that is, the protein is allowed to relax in the presence of a perturbation due to the ligand-protein interaction. A detailed description is obtained for the displacements of residues required for the ligand to enter or leave the globin. The barrier heights calculated in this manner are found to be in qualitative agreement with observed values. Some differences between myoglobin and hemoglobin are described. Although the present calculations make use of a simplified model of the ligand-myoglobin system, they provide a useful first step in the analysis of the effect of the globin matrix on the binding process. © 1979.