[HN Gopher] Foldit
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       Foldit
        
       Author : tosh
       Score  : 44 points
       Date   : 2024-02-18 16:55 UTC (6 hours ago)
        
 (HTM) web link (en.wikipedia.org)
 (TXT) w3m dump (en.wikipedia.org)
        
       | Havoc wrote:
       | I used to participate in the folding at home project. Not sure it
       | makes sense post alphaFold. Is this not a solved problem now?
       | 
       | Or does additional compute still matter?
        
         | humnre wrote:
         | > Is this not a solved problem now?
         | 
         | This is an interesting question.
         | 
         | Can any contemporary "ai" solution be considered a solved
         | problem?
         | 
         | A lot of these neural net architecture are designed first and
         | foremost as approximation engines without any guarantees the
         | provided approximation is even any good.
         | 
         | This can be useful, but especially in a medical sense, also
         | insufficient or even dangerous.
         | 
         | > AlphaFold's protein structure prediction results at CASP were
         | described as "transformational" and "astounding".[93][94] Some
         | researchers noted that the accuracy is not high enough for a
         | third of its predictions, and that it does not reveal the
         | mechanism or rules of protein folding for the protein folding
         | problem to be considered solved.[95] Nevertheless, it is
         | considered a significant achievement in computational
         | biology[92] and great progress towards a decades-old grand
         | challenge of biology.[93]
         | 
         | https://en.m.wikipedia.org/wiki/Protein_folding
         | 
         | Protein folding is still very much an unsolved problem.
        
         | COGlory wrote:
         | What AlphaFold is doing is essentially matching a sequence of
         | amino acids to solved protein structures, albeit dynamically,
         | and with some advanced constraints. In essence, it's not
         | predicting how the protein will fold, but rather, how the
         | protein will look once it's done folding. And in many many
         | cases, there's no matching fold for a sequence.
         | 
         | Also, proteins are dynamic. They interact with other proteins.
         | They sample multiple conformations, they frequently rearrangle,
         | or become disordered, and then re-ordered. AlphaFold is just a
         | single snapshot.
         | 
         | If we want to understand how proteins fold, we need more than
         | just AlphaFold.
        
       | samtho wrote:
       | Link to project: https://fold.it/
       | 
       | Biochemistry mystifies me in same way that most other sciences to
       | do not. It's amazing to me that they can, in theory, derive
       | useful insight or scientific leads from people playing.
       | 
       | Does anyone have an ELI5 on why/if this is more efficient than
       | just iterating through combination programmatically?
        
         | synapsomorphy wrote:
         | The goal of most/all machine learning is hunting down
         | performance maxima in a super high dimensional space. In this
         | case the space is the positions and angles etc of the atoms
         | that comprise a protein and the "performance" is the stability
         | of the protein.
         | 
         | For the number of atoms that comprise most proteins, iterating
         | through all the possible positions would take an unimaginable
         | amount of time, so you have to have some kind of search method
         | to identify good position-space-areas to investigate more
         | closely.
         | 
         | My guess as to where people help in is getting away from bad
         | local maxima. In my experience playing foldit, sometimes you
         | can see pretty clearly that the stability is not good and it's
         | not going to get much better with small changes - the algorithm
         | has found a bad local maxima of performance - so you can
         | manually move big chunks of the protein around to explore a new
         | part of the position-space. This kind of evaluation, knowing
         | when to stop climbing a small hill and instead go looking for
         | bigger hills, seems to be something that humans are pretty
         | decent at. Of course there's also a million algorithms to do
         | the same thing without humans.
        
           | COGlory wrote:
           | Just a nitpick, we typically call it a local minima, because
           | we are trying to minimize energy. A stable protein will be at
           | (or near) the minimal energy conformation.
           | 
           | Otherwise, I think you are absolutely correct. It's a nearly
           | infinite computational problem that has a tendency to
           | overfit. There are all sorts of ways to try to solve this
           | problem, but they don't always work as well in all cases.
        
             | synapsomorphy wrote:
             | Yeah, it's actually a loss function minima, just trying to
             | ELI5ify it a bit.
        
           | web007 wrote:
           | The added benefit of FoldIt is to see _how_ humans find a
           | better answer than naive  "shake" and local minima/maxima.
           | Those methods can then be integrated into automation to get
           | better results. So it's not just "people are better at this,
           | let them do the work" it's "let's get people to show their
           | work" and then use that process to make better tools.
        
       | el_benhameen wrote:
       | If you misfold the proteins, does it spread to other users and
       | crash the game?
        
         | amarant wrote:
         | Depends. If you manage to fold a prion it will spread to other
         | users and corrupt their memory, introduce odd rendering
         | artifacts and finally brick their computer.
         | 
         | ;)
        
       | harveywi wrote:
       | They missed an opportunity to call it Texas Fold 'Em.
        
         | recursive wrote:
         | From Washington though.
        
       | schappim wrote:
       | This is like Ender's Game for protein folding.
        
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