Related to this, transition state geometries and solvent penetration of the active site (Table ), as well as electrostatic contributions of individual amino acids to catalysis (Figure and Table ) are virtually unchanged between wild-type YopH and the chimeric constructs (the largest ~ 1 kcal mol -1 difference comes from residue 357, which is a Gln in wild-type YopH, and a Phe in Chimeras 2, 3, and the corresponding position in wild-type PTP1B). This is perhaps unsurprising because no active site residues were perturbed upon creation of these constructs, and our simulations emphasize that, were the Chimeras to be able to achieve optimal closed conformations of the WPD-loop, they would be expected to show similar turnover numbers to the parent enzymes.