Dominant features of protein reaction dynamics: conformational relaxation and ligand migration.

Here, we review the dominant aspects of protein dynamics as revealed by studying hemoproteins using the combination of laser flash photolysis, kinetic spectroscopy and low temperature. The first breakthrough was the finding that geminate ligand rebinding with myoglobin is highly non-exponential at temperature T<200 K, providing evidence for the trapping of a large number of protein statistical substates. Another major advance was the introduction of a "model free" approach to analyze polychromatic kinetics in terms of their rate spectrum rather than to fit the data to some arbitrarily predefined kinetic scheme. Kinetic processes are identified and quantified directly from the rate spectrum without a priori assumptions. In recent years, further progresses were achieved by using xenon gas as a soft external perturbing agent that competes with ligand rebinding pathways by occupying hydrophobic protein cavities. The first part of this paper introduces several basic principles that are spread throughout a vast literature. The second part describes the main conclusions regarding conformational relaxation and ligand migration in hemoproteins obtained by combining these approaches.