Figure 4. The proposed molecular mechanism for epimerization reaction catalyzed by NocTE. The direct deprotonation path and re-protonation path Path1 were colored in pink and green. The abbreviations R, TS, IM and P represented the reactant, transition state, intermediate and product.
To shed light on the detailed mechanism of this special epimerization, QM/MM calculations were performed using the cluster model on the basis of three structure replicas from the dominant cluster of MD simulations. Geometry optimizations, TS search and IRC calculations were carried out at the ONIOM (M062X/6-31G*: Amber) level. Then single point energies were calculated with larger basis set 6-311+G** and SMD solvation model to obtain more accurate energy profile. The free energy profile and important TS structures from the representative replica were displayed in Figure 5. Other minimum structures and two replicas were provided in Figure S8, Table S4 and Table S5.