5G1Y ). The first and last of these variants are only active towards the isomerization of PRA, whereas the middle two variants are bifunctional towards both PRA and ProFAR (Table ). In all cases, when performing conventional MD simulations starting from the closed conformation of loop 1, this loop is very stable, and remains closed over our simulation timescales (Table ). We From analysis of our MD simulations (Table ), we clearly see how all variants carrying the D10G substitution are able to populate all three of closed, open and wide-open conformations.