Figures S8A and B identify three major regions (the WPD-loop, the β5-and β6-strands, and the α7-helix) where there is a significant difference in RMSF values between wild-type YopH and Chimera 3. Consistent with the RMSD data, the closed WPD-loop conformation is more stable in wild-type YopH as compared to Chimera 3, especially at the central portion of the WPD-loop. To understand why these regions are more stable in wild-type YopH, we determined how the noncovalent interaction networks differed in both proteins using our recently developed package, Key Interactions Finder (KIF, ). The results obtained from KIF are presented in Figures S8C, S8D and S10. By analysing these differences, we identified the T358G substitution resulted in the removal of two inter-WPD-loop hydrogen bonding interactions with W354 and P355. This helps to explain the likely decrease in stability of the central portion of the WPD-loop, as a result of this substitution.