Bimolecular and geminate molecular oxygen (O 2) rebinding to isolated α chains of human adult hemoglobin in solutions is analyzed. Multiple extended molecular dynamics (MD) simulations of the O 2 migration within the protein after dissociation are described. Computational modeling is exploited to identify hydrophobic pockets within the α chains and internal O 2 migration pathways associated with the experimentally observed ligand rebinding kinetics. To initiate dissociation, trajectories of the liganded protein are interrupted, the iron–dioxygen bond is broken, and the parameters of the iron–nitrogen bonds are simultaneously altered to produce a deoxyheme conformation. MD simulations provide 140 essentially independent trajectories (up to 25-ns long) of the O 2 migration in the protein. The time dependence of cavities occupancy, obtained by the MD simulations, and the kinetics of O 2 rebinding, measured by flash-photolysis techniques, allow us to obtain the kinetics of the entire O 2 migration process within the nanosecond time range and construct an explicit kinetic model of the O 2 migration and rebinding process. The amino acids that have the most pronounced effect on the ligand migration within the α chain matrix are predicted.