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Just to add to this whole "It's not solved! Yes it is!" discussion. Note that >According to Professor Moult, a score of around 90 GDT is informally considered

Just to add to this whole "It's not solved! Yes it is!" discussion. Note that >According to Professor Moult, a score of around 90 GDT is informally considered to be competitive with results obtained from experimental methods. So if we go by >= 90 as solved: >In the results from the 14th CASP assessment, released today, our latest AlphaFold system achieves a median score of 92.4 GDT overall across all targets. they solved for their targets, but >Even for the very hardest protein targets, those in the most challenging free-modelling category, AlphaFold achieves a median score of 87.0 GDT (data available here). They basically admit they still haven't "solved" it for "most challenging free-modelling category" Take that as you will, not sure how useful the ">= 90 is solved" criteria is since they call it "informal" themselves.

pretendscholar 6y ago
87 GDT sounds pretty much solved to me if 90 is the benchmark
garmaine 6y ago
That’s shifting goal posts. The hardest structures are also going to be harder experimentally. What makes them hard to predict is the very close energies involved in different folding pathways. Those close energies mean there will be more variant structures which change by use the experimental approach too.
deleted 6y ago
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fastball 6y ago
What do you mean you're not sure how useful ">= 90" is as a criteria? You literally said why it is useful in your comment: > 90 GDT is informally considered to be competitive with results obtained from experimental methods. It's informal because we don't have a true "gold-standard" for determining a protein's folded structure – the best we have is experimental methods of trying to determine the structure which still have a great deal of error (compared to other things we can measure). So all we can do is say "the GDT between two experimental measurements (of the same protein) is often around 90, so if we get there with predictive models that's pretty much just as good". As soon as we have better experimental methods for determining protein tertiary structure, you can be sure we will require predictive models to deliver better results too. Until then, the point is that the delta between any two experimental determinations of folded structure is approximately the same as the delta between an experimental determination and an AlphaFold guess. So the AlphaFold guess may as well be an experimental measurement. Except the AlphaFold guess happens fairly trivially (once you give it the DNA sequence[1]), where as the experimental method is involved and expensive. [1] Or the primary structure, I'm unsure what inputs are given to AlphaFold.
vadansky 6y ago
Just to add to my own comment. Why does HN like being so pedantic about the definitions of words? This is an interesting post regarding AI and cellular biochemistry. Do we really need to add a philosophical debate about the meaning of "solution"? Personally I think anyone who can't add to the discussion about AI and protein folding should just not comment, instead of settled on adding to the what does solution mean "debate". I'd love to see a blanket rule flagging pedantic posts.
- 6gvONxR4sf7o 6y ago
  HN pushes back on hype and because there's generally too much hype in announcements.

pretendscholar 6y ago

87 GDT sounds pretty much solved to me if 90 is the benchmark

garmaine 6y ago

That’s shifting goal posts. The hardest structures are also going to be harder experimentally. What makes them hard to predict is the very close energies involved in different folding pathways. Those close energies mean there will be more variant structures which change by use the experimental approach too.

deleted 6y ago

[deleted]

fastball 6y ago

What do you mean you're not sure how useful ">= 90" is as a criteria? You literally said why it is useful in your comment: > 90 GDT is informally considered to be competitive with results obtained from experimental methods. It's informal because we don't have a true "gold-standard" for determining a protein's folded structure – the best we have is experimental methods of trying to determine the structure which still have a great deal of error (compared to other things we can measure). So all we can do is say "the GDT between two experimental measurements (of the same protein) is often around 90, so if we get there with predictive models that's pretty much just as good". As soon as we have better experimental methods for determining protein tertiary structure, you can be sure we will require predictive models to deliver better results too. Until then, the point is that the delta between any two experimental determinations of folded structure is approximately the same as the delta between an experimental determination and an AlphaFold guess. So the AlphaFold guess may as well be an experimental measurement. Except the AlphaFold guess happens fairly trivially (once you give it the DNA sequence[1]), where as the experimental method is involved and expensive. [1] Or the primary structure, I'm unsure what inputs are given to AlphaFold.

vadansky 6y ago

Just to add to my own comment. Why does HN like being so pedantic about the definitions of words? This is an interesting post regarding AI and cellular biochemistry. Do we really need to add a philosophical debate about the meaning of "solution"? Personally I think anyone who can't add to the discussion about AI and protein folding should just not comment, instead of settled on adding to the what does solution mean "debate". I'd love to see a blanket rule flagging pedantic posts.

6gvONxR4sf7o 6y ago
HN pushes back on hype and because there's generally too much hype in announcements.