The binding free energy decomposition of residues (Figure ) shows that energy contribution of N501 in RBDWT is -2.12 ± 1.13 kcal/mol, while the energy contribution of Y501 in RBDOmicron is -6.97 ± 0.30 kcal/mol (a stronger attraction). By analyzing molecular dynamic trajectories, we found that Y501RBD and Y41ACE2 could form a strong π-π stacking interaction (Figure ). As shown in Figure , the center of mass distance between Y501RBD and Y41ACE2 is around 5.5 Å throughout the 200ns trajectory.