In order to understand the detailed implications of every mutation on the binding to ACE2, we conducted binding free energy decomposition based on all nine 50-150ns trajectories. As indicated in Figure , we found that although there were some fluctuations in the three experiments, the energy contributions of residue 498, 493, 505, and 496 in Omicron variant RBD are smaller than that in WT especially for residue 498.