While loops 5 and 6 of HisA and PriA have been clearly identified as being important for binding and catalysis (loop 6 carries the catalytic aspartic acid side chain, Figure ), the precise catalytic role of loop 1 remains unclear, although extending the conformation of loop 1 through duplication of residues 13-15 (HisA(dup13-15)) plays an important role in the acquisition of bifunctionality in a real-time evolution experiment on HisA, and substitutions at position 15 on this loop appear to be important for facilitating the TrpF activity of this enzyme. Therefore, we also performed simulations of the SeHisA(dup13-15/D10G) variant, as described in the Methodology section. SeHisA(dup13-15/D10G) is a bifunctional enzyme that can catalyze the isomerization of both ProFAR and PRA with modest catalytic efficiencies, and the corresponding crystal structure (PDB ID: 5AC7 ) shows the enzyme in a 'PRA-active' conformation with loops 1 and 6 in a closed state, and loop 5 in an open state.