To further probe the role of loop 1 in HisA and PriA, we have complemented our conventional and enhanced sampling molecular dynamics simulations with empirical valence bond (EVB) simulations of the initial ribose ring opening step in the Amadori reaction of substrates ProFAR and PRA (Figure ), as catalyzed by wild-type and variant forms of the two enzymes (see the Methodology section for details of the simulation and parameterization procedures).