TABLE 3.

Comparison of literature observations and MD

Observation	Reference	Experimental dataa	MD simulations in the current study
N370S pH optimum of 6.2	25	+	N370S less flexible, loop 1 stabilized, better loop 1 and 3 interaction, active site geometry more often correct
Loop 3b destabilized at pH 4.5	35	−	Destabilization
NB-DNJ stabilizes GCase WT and N370S	58	+	Stabilization
In crystal structure with chaperones, loops 1 and 3 interact less well	35	+	Less interaction for bound NB-DNJ+
Secondary structural change in loop 3	35	+	For N370S, changes are observed at pH 4.5
The activity of N370S at higher pH is similar to the activity of WT at lysosomal pH	40	+	Similar trend in the active site configuration and the arrangement of loops 1 and 3
Loop 3 interacts less with the N370S helix, which might favor interaction between residues 315 and 366	35	−	Confirmed in MD simulations
3 orders of magnitude more IFG needed to increase activity of WT compared to N370S	25	+	The affinity of unprotonated NB-DNJ at pH 7.4 is lower for the WT than for N370S
N370S reduces the interaction of GCase and SapC, which can be reversed by IFG	25, 38	+	Interaction with SapC is likely to be disrupted but can be restored by binding of NB-DNJ+

^a The availability of experimental data is indicated by a plus sign, and lack of experimental data by a minus sign; the information is based on analysis of GCase crystal structures.

^b In Ref. 35, loop 3 is referred to as loop 1.