Insight into the Predictive Binding Modes of the Influenza a Neuraminidase in Complexes with Avian and Human Receptor Analogues

The binding modes of the influenza A(H7N9) neuraminidase in complexes with avian-type (3′-SLN) and human-type (6&prime-SLN) receptor analogues are investigated by combined homology modelling, molecular docking and quantum mechanical/molecular mechanical (QM/MM) methods. The results reveal that these two analogues could be docked into the active site surrounding by residues of R118, T148, R152, E227, R276 and R371, and bind well in the receptor binding site. Comparing with the docking results, we find that the stabilities of the binding modes are all strengthened after optimisation. However, human-type 6′-SLN might be a preferable receptor analogue as it generates more HB interactions. Whether in the docking results or in the optimised structures, both of analogues (3′-SLN and 6′-SLN) bind in the receptor binding site mainly using their sialic acid groups of the analogues. This conclusion is consistent with most experimental results obtained from crystal structures. Our results give a good understanding on how the N9 interacts with host receptors from a structural perspective. They support the conclusion that the receptor binding mode might be changed from a avian-type to human-type receptor binding. This result might provide a theoretical guide for the study of the influenza A (H7N9) in the future.