Ligand diffusion in globins: simulations versus experiment

Computer simulations in molecular biophysics describe in atomic detail the structure, dynamics, and function of biological macromolecules. To assess the quality of these models and to pick up new mechanisms, comparisons with experimental measurements are made. Most comparisons examine thermodynamic and average structural properties. Here we discuss studies of dynamics and fluctuations in a protein. The diffusion of a small ligand between internal cavities in myoglobin, and its escape to solvent are considered. Qualitative and semi-quantitative agreements between experiment and simulation are obtained for the identities of the cavities that physically trap the ligand and for the connections between them. However, experimental and computational ‘doors’ are at significant variance. Simulations suggest multiple gates while kinetic experiments point to one dominant exit.