Biophys. J. 110, 218–233 (2016)

When bird flu became transmissible between mammals, the mutation was surprisingly slight: a 1.4-fold increase in molecular binding affinity at the interface between the virus and its host. Now it seems thermodynamics might be able to tell us why. Huafeng Xu and David E. Shaw have devised a model for biological adhesion, which suggests that small changes in these affinities can give rise to larger increases in adhesion affinity — enough, perhaps, to switch the virus' binding preference from avian to mammalian cells.

Similar models have been used to describe interactions on a molecular level, where there are only a handful of binding pairs. But when a virus invades a host cell, the contact area often covers hundreds — if not thousands — of binding sites. Xu and Shaw took advantage of this to invoke approximations appropriate for many interactions. They estimated affinities consistent with those measured in experiments, and uncovered a mechanism by which weak binding may be amplified to facilitate high-affinity adhesion.

The study could help us stem the spread of influenza via competitive inhibition, which reduces the number of available connection sites. The authors' model suggests that even a relatively weak inhibitor could compromise adhesion in this way.