Fig. 3. Contribution (tICA coefficient) of the selected residues for the slowest dynamics of the system in the ground state (GS, black) and transition state (TS2, red). The contributions of R396, E399 and L407 are 0.014, 0.010 and 0.015, respectively, in the GS state, while they are 0.018, 0.015 and 0.019, respectively, in TS2. The big differences between the ground state and transition state observed in HMG-CoA and NADH are coming from those selected heavy atoms around the transferring hydrogen that were treated by TSFF in the TS2 state. The “HMG-CoA” and “NADH” labels in the x-axis denote the heavy atoms of the substrate and cofactor respectively, “small/large domain” denotes the Cα atoms of the residues that contact with HMG-CoA/NADH in the small and large domain, and “flap domain” denotes the Cα atoms of the residues (374 to 428) in the hinge region and flap domain.