Molecular dynamics (MD) simulations of wild-type (WT) PTP1B as well as the soluble proteins Chimeras 1, 3, 4 and 7, were performed using the Amber 2018 62 simulation package. All simulations were performed in the phosphoenzyme intermediate, which represents the reactive species for the rate-determining second chemical step (Figure ). NMR dynamics measurements on this species are not feasible due to its transient existence in solution. Simulations were performed for each enzyme starting from both the WPD-loop closed and open conformational states, using the PDB 63 structures outlined in Table for each system and state. Simulation starting structures of WT PTP1B were prepared as described previously, and Chimeras 1, 3, 4 and 7 were also prepared using the available crystal structures from both this and a previous study where possible. For simulations of systems with no available crystal structure, the most closely related (in terms of WPD-loop sequence) crystal structure was modified (through PyMOL mutagenesis) to generate the starting structure (no more than three mutations were required for any system, see Table for further details).