Comment by flobosg
2 years ago
> Yes, it has a very nice model of what sequences should look like in 3D.
A structural model, you would say.
> That model is derived from experimental data.
That doesn’t make it a template-based model, or a homology one.
> if I give AlphaFold an MSA of a new, unknown protein fold (substantively away from any known fold), it cannot predict it
That will depend on the number of effective sequences found to derive couplings. Domains with novel folds usually have a low number of remotely homolog sequences and for that reason the method will fail, not just because they are novel.
>Domains with novel folds usually have a low number of remotely homolog sequences and for that reason the method will fail, not just because they are novel.
How can you say this but not believe it's doing homology modeling?
Because homology search is not homology modelling. And a multiple sequence alignment is not a structural (i.e, with three-dimensional coordinates) template.
For someone who knows very little about this field, could you elaborate on what specific aspect of “homology modeling” AF violates/circumvents which makes you call it “homology search” instead?
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