Simulations were performed on wild-type SeHisA, MtPriA and TmTrpF, as well as relevant enzyme variants, in both their unliganded forms and in complex with various ligands (substrates ProFAR and PRA and, in the case of the enhanced sampling simulations, products PRFAR and CdRP). A total of fourteen crystal structures were used to generate starting points for these simulations, and all simulations performed as well as associated structures used are summarized in Table . Where present, the D7N, D11N and D176A substitutions were reverted to wild-type using the Dunbrack 2010 Rotamer Library, as implemented in UCSF Chimera, v. 1.14. Missing regions in the catalytic loops were reconstructed using Modeller v. 9.23. The catalytic aspartic acid side chain in the active site of each enzyme (D176 in HisA, D175 in PriA and D126 in TrpF)