How does one predict how large of an effect on antigenic drift a substitution in the amino acid sequence of a surface protein of influenza has?

Question

I know that some amino acid substitutions are more effective in causing antigenic drift than other substitutions based on their location in the 3d structure of the HA protein (proximity to the receptor binding site).

I would like to be able to determine using a program whether a virus will be dominant based on multiple factors including genetic difference from the previously dominant virus. How can one know how much bigger of an effect one AA substitution will have on the antigenicity of a virus compared to another?

Any help is much appreciated.

Answer 1

Your understanding of influenza antigenic drift is, unfortunately, hypersimplified and mostly wrong. In particular, your notion that some mutations are more important for antigenic drift because of their effects on structure is at best oversimplified.

Rather than spend many paragraphs reviewing the complex patterns involved, I'd suggest you start by carefully reading papers from people who have correlated antigenic drift with sequence change, such as

• Sequence-Based Antigenic Change Prediction by a Sparse Learning Method Incorporating Co-Evolutionary Information
• Using Sequence Data To Infer the Antigenicity of Influenza Virus
• Mapping the Antigenic and Genetic Evolution of Influenza Virus
• The genomic and epidemiological dynamics of human influenza A virus
• Selection of antigenically advanced variants of seasonal influenza viruses
• Antibody landscapes after influenza virus infection or vaccination
• Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

This is a field that a lot of extremely smart people have been looking at extremely closely for many years; all the simple approaches have been tried already.