Abstract:
Dynamics of antigenic and host receptor binding behavior of a virus binding protein can be altered via mutations that lead to escape from immune recognition. The main focus of this study is to investigate the dynamic behavior of Influenza A virus Hemagglutinin (HA) of the 2009 human pandemic H1N1 in comparison to other H1N1 strains, by Molecular Dynamics (MD) simulations. HA is the host receptor binding protein that has a key role in virus-host interaction. The dynamic behavior of HA of two Influenza A (H1N1) variants and their mutants at residue position 149 were studied comparatively between the structures to search for the effect of this position between the two variants (K149 and R149) and the mutations (K149R and R149K) with the emphasis on the Receptor Binding Domain (RBD) of HA. The residue 149 is chosen considering its importance due to being a discriminating position between classical (R149) and 2009 pandemic (K149) swine viruses, although it is directly associated with neither antigenic nor sialic binding sites. Residue 149 is also identified as one of the hinge positions in both of the variants within their wild and mutant types, implying an allosteric dynamic affect. The position 149 is found to be highly affecting the dynamics of RBD at 130 loop and 220 loop that includes the receptor binding site (RBS) residues 134-138 and 221-228 as well as antigenic binding sites (Sa and Ca), which is particularly strong for K149. The structures of K149 and R149K displaying more restricted mobility lead to a higher cooperativity and efficient global HA behavior. Overall, the results imply that allosteric dynamic effect of 149 may affect virulence as a result of altering dynamic behavior in RBD of HA.
