Based on the extended MD trajectories, the RMSF of the protein's heavy atoms and the dynamic cross-correlation matrix (DCCM) of the protein's Cα atoms were calculated via the CPPTRAJ program 50 . The alignment of trajectories to the first frame was conducted prior to the RMSF and DCCM calculations. Residues that made a < -1 kcal/mol contribution to MM-GBSAbinding free energy were categorized as energetically important residues. Residues that showed clear RMSF changes (ΔRMSF > ~0.5 Å) and significant correlation changes (as evidenced by DCCM analyses) upon small molecule binding were identified as potential allosterically important residues. Collectively, these energetically and allosterically important residues were identified as key residues for enzyme catalysis.