We note that in both cases an exceptionally high pK a for E18 is predicted. While previous work on DJ-1 has suggested that E18 is protonated over the titration regime of C103 and glutamate residues have been reported with pK a values greater than 9, 62 it would seem improbable that the pK a is actually this high. Structurally, a second glutamate (E18) and a nearby histidine (H126) likely play roles within the lower pH regime (i.e., < 7). We preface the following section by noting that a high glutamate pK a value is also suggested by the CpHMD simulations and PropKa as described further.