where [S] Zero distance corresponds to the active site non-heme Fe atom. In the case of variant I204T, the identified tunnel consists of inflexible side-chain residues near the surface resulting in a lower-bound trajectory that is excessively elevated close to the surface. Note the issues with calculations of binding energies calculations for variant I204T mentioned in the text. databases. However, all protein variants of interest were detected in all major types of environments (e.g., marine, freshwater, terrestrial) sampled. Overall, these results indicate that the RDO variants examined in this study are not only products of laboratory evolution but also have arisen through natural evolutionary processes in the environment.