O₂ free energy landscape obtained from the ILS calculations and lowest free energy pathways obtained from the ILS energy landscape.

<p><b>A-</b>O₂ free energy landscape obtained from the ILS calculations. Two isosurface contours are shown, with free energy levels at -5 (blue inner contour) and 5 (cyan contour) kJ·mol⁻¹. <b>B-</b> Comparison of the O₂ free energy landscape obtained from the ILS calculations (blue maps) and high-affinity regions from the O₂ explicit MD simulations (red maps). The probability density contours at 0.00015 Å⁻³ are represented as a red isosurface. <b>C-</b> O₂ lowest free energy pathways obtained from the ILS energy landscape. The spheres represent the local free energy minima while the tubes connecting the minima represent the pathways. The size of the spheres representing the local energy minima scales linearly along the displayed free energy range (small spheres indicates high free energy while large spheres indicate low free energy). The diameter of the pathways scales linearly with the free energy and thus with the oxygen affinity (thinner radius represent high free energies and low oxygen affinity). The free energy at the minima and along the pathways follows the same color scale. The channel 1 coincides with the channel inferred from the X-ray data <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004010#pcbi.1004010-Tsukihara1" target="_blank">[7]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004010#pcbi.1004010-SvenssonEk1" target="_blank">[13]</a> whereas the channel 2 and channel 3 are alternative routes to reach the BNC.