by Vasily Unguryan | Novosibirsk State University, State Research Center of Virology and Biotechnology
VECTOR
Motivation and Aim: The surface protein of the influenza virus, hemagglutinin, plays a key
role in the virus entry into the cell. When infecting a cell, the virus first binds to a receptor
on the cell membrane surface, followed by the capture of the virus inside the cell. The
influenza virus infectivity is defined by the duration of binding persistence, which is related
to energy characteristics of the bonds.
The new group of A(H3N2) influenza virus serotype, the Bangladesh group, has spread in
recent years in Russia, replacing other groups of this serotype. The aim of this work was to
compare the binding properties of Bangladesh group representatives with the international
reference strain of A(H3N2) subtype in the complex with the human receptor analog 6′-
sialyl-N-acetyllactosamine.
Methods and Algorithms: The initial structures of hemagglutinins under study were
modelled with MODELLER with the template of the known structure H3N2 from the Protein
Data Bank (sequence identity 95%, code PDB 6bkt). The molecular dynamics simulations
were performed using NAMD during 4 nanoseconds to determine more precisely the
orientation of the model side chains and receptor position. The structures of the time
interval from 3 to 4 nanoseconds with the time step of 1 picosecond were sampled for the
subsequent docking analysis using the AutoDock Vina program.
Results: During the molecular dynamics simulations, the receptor analog was in the correct
stable binding conformation. Docking analysis allowed a numerical estimation of the free
energy of protein binding to the receptor analog. A histogram was built for the data
obtained (figure 1). For a protein and the receptor analog prepared as rigid structures, the
free energy estimate is 11.27 kcal/mol for the reference system and 12.7 kcal/mol for the
Bangladesh group representative, with the standard deviation being 0.5 kcal/mol and 0.56
kcal/mol, respectively.