O2 migration pathways are not conserved across proteins of a similar fold.

Recent advances in computational biology have made it possible to map the complete network and energy profile of gas migration pathways inside proteins. Although networks of O(2) pathways have already been characterized for a small number of proteins, the general properties and locations of these pathways have not been previously compared between proteins. In this study, maps of the O(2) pathways inside 12 monomeric globins were computed. It is found that, despite the conserved tertiary structure fold of the studied globins, the shape and topology of O(2) pathway networks exhibit a large variability between different globins, except when two globins are nearly identical. The locations of the O(2) pathways are, however, found to be correlated with the location of large hydrophobic residues, and a similar correlation is observed in two unrelated protein families: monomeric globins and copper-containing amine oxidases. The results have implications for the evolution of gas pathways in proteins and for protein engineering applications involving modifications of these pathways.