ACS Catalysis (2021), 11, 3182 - 3189
DOI: https://doi.org/10.1021/acscatal.0c05193
In a recent paper, we have shown that variations in tunnel geometry affect the specificity of biological oxidations, leading to increased activity and altered selectivity, as well as an expanded substrate scope. In this paper, we study the second main strategy that can confer specificity to the orientation and anchoring of a substrate. Through molecular modeling and MD simulations, we gained deeper insights into enzyme dynamics and demonstrated that anchoring of the substrate and reducing the protein scaffold flexibility is a critical factor for increased efficiency of this enzyme towards the terminal hydroxylation of octanoic acid.