1 Department of Chemistry and Biochemistry, Centre for Research in Molecular Modeling and PROTEO, Concordia University , Montreal, Quebec H4B 1R6, Canada.

Atomistic molecular dynamics simulations of diffusion of O2 from the hemes to the external solvent in the a- and ß-subunits of the human hemoglobin (HbA) tetramer reveal transient gas tunnels that are not seen in crystal structures. We find here that the tunnel topology, which encompasses the reported experimental Xe binding cavities, is identical in HbA's T, R, and R2 quaternary states. However, the O2 population in the cavities and the preferred O2 escape portals vary significantly with...