When it comes to occupancy frequencies of key residues among 11 systems, there are 14 residues that have direct interaction with 3 or more antibodies, and 9 residues, concentrating in residues 144-147 and 246-252, that play an important role in 5 or more systems (Figure ). In particular, Y144 is involved in almost all mAbs binding except DH1052 (PDB ID: 7LAB), and the mutants of Y144 like Y144del and Y144F are already present in the real world . Y144, K147, R246 and Y248 make a relatively large contribution in 8 or more antibodies binding, hinting mutations of these four residues have the high possibility to affect binding affinities of most NTD mAbs. Thus, we should pay special attention to these sites when optimizing antibodies to NTD.