In the present work, we combine conventional and targeted molecular dynamics simulations with empirical valence bond simulations to characterize both the transition state for the ratelimiting hydrolysis step catalyzed by Chimeras 2 and 3, as well as the dynamical properties of the WPD-loops of both YopH chimeras. We observe negligible energetic differences between the chemical steps of the different enzymes, but significant differences between their WPD-loop dynamics, and provide insight into the detailed molecular interactions driving these differences.