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I have read the scientific paper, "Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution" by Björn F. Koel et al (http://science.sciencemag.org/content/342/6161/976).

In the paper, important positions to influenza antigenic drift include positions 109-301, with special emphasis on sites 133, 144, 145, 155, 156, 158, 159, 189, 193.

However, nowhere in the paper does it specifically mention which positions are part of the receptor binding site and which are close to it.

The range (109-301) is a bit broad since it includes amino acid positions that are unimportant to antigenicity. I would like a list of all very important AA substitutions (that are near the receptor binding site) to involve in a bioinformatics project. The special emphasis amino acid sites list does not include all amino acids that are near the binding site.

To convey a sense of the problem, if position 155 is important, does that mean position 156 is also important?

I don't know if position 156 is considered "near" the receptor binding site.

Any help is appreciated.

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  • $\begingroup$ I may provide a more substantial answer after reading the paper but right now I just want to point out that an amino acid substitution can affect sites that are far from it (on the sequence) because it can affect the folding. There are no general rules but some approximations can be made if we know the protein structure. $\endgroup$ – WYSIWYG Jan 8 at 11:46
  • $\begingroup$ @wysiwyg that's a fair point in general but less of an issue with influenza hemagglutinin. HA is incredibly tolerant of amino variants and can include a shocking number of substitutions without drastically affecting its folding. The result is that it's usually fairly safe to consider mainly local effects of substitutions without worrying too much about major structural changes $\endgroup$ – iayork Jan 8 at 19:10
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Short answer: Yes, 156 is generally considered "near" the RBS, e.g. in this paper you can see it mapped onto the structure.

For a more general answer, you'll need to sit down and stare at 3D models of hemagglutinins (there are hundreds in the PDB), just like the rest of us. Antibody binding sites are not black and white, and interactions between influenza and antibodies are wildly complicated. What's "near" in some contexts might be "far" in others.

You might find the Influenza Research Database's Identify Sequence Features in Segments tool useful, particularly its annotation of hemagglutinin H3.

Be aware that numbering of amino acids can be confusing, since different groups may be using different starting points. There's a vague agreement on the "correct" numbering, but quite a few groups pay it lip service and then number their version however they like.

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