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 O₂ 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 O₂ 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 O₂ pathway networks exhibit a large variability between different globins, except when two globins are nearly identical. The locations of the O₂ 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.