Extended Data Fig. 6: Molecular dynamic simulation of 7 in the PdxI active site.

Distances over time of hydrogen bonds to the various positions of the pyridone are tracked in chain A (a) and chain B (b) of the active site. Left panels show H336 and K337 form hydrogen bonds to the 4-position substituent on the pyridone ring. Right panel shows Q412 and H161 remain hydrogen bonded to 2-position substituent and pyridone nitrogen N1, respectively, for the majority of the simulation. c, Molecular dynamic simulations were initiated from an extended conformation (dihedral = ~180°). Over time, we monitored this conformation to see if the alkyl chain could spontaneously fold to a reactive conformation (dihedral = –20°). Indeed, for short durations of the simulations we observe the chain folding into a reactive conformation for a pericyclic reaction.