In order to understand the underlying mechanism of R246I mutation, we carried out a more detailed analysis for the trajectory of glycosylated NTD-(5-24) complex (PDB ID: 7L2F). Through energy decomposition of per residue, we found that R246 has a large negative value (-9.95±1.28 kcal/mol), while I246 has an energy contribution close to zero (-0.15±0.07 kcal/mol), which illustrates I246 has much less contact with 5-24 compared with R246 (Figure ). What's more, the contribution of residue D105 in 5-24 tends to be reversed before and after the mutation (Figure ), suggesting that R246 are in close contact with D105.