As can be seen from Fig. 4 , the result obtained from the docking simulation has proved that the compound binding interactions with residues ARG227 and ASP92 were fully consistent with the previous report [57] . The structure of Neo6 complemented the shallow pocket of HA1 with the optimal conformation. The side chains of the key residues, such as Arg227, Pro143, Glu72 and Asp92 in protein, made a major contribution to the receptor-ligand binding affinity by forming H-bonds with the different heavy atoms (e.g. O, N) of the Neo6 (Fig. 4) . Besides the common H-bonds formed between the three residues (Arg227, Pro143, and Glu72) and the compound Neo6 as in [58] , the other two H-bonds were formed between the two nitrogen atoms of the new extensible fragment core4 and the oxygen atom of Asp92 residue. Consequently, compared with ZINC01602230, the binding affinity of Neo6 with the receptor was strengthened from 25.83 kcal/mol to 28.38 kcal/mol (Fig. 3 ).