> Alphafold made a breakthrough in protein folding.
Sort of. Alphafold is a prediction tool, or, alternatively framed, a hypothesis generation tool. Then you run an experiment to compare.
It doesn't represent a scientific theory, not in the sense that humans use them. It does not have anywhere near something like the accuracy rate for hypotheses to qualify as akin to the typical scientific testing paradigm. It's an incredibly powerful and efficient tool in certain contexts and used correctly in the discovery phase, but not the understanding or confirmation phase.
It's also got the usual pitfalls with differentiable neural nets. E.g. you flip one amino acid and it doesn't really provide a proper measure of impact.
Ultimately, one major prediction breakthrough is not that crazy. If we compare that to e.g. Random Forest and similar models, the impact in science is infinitely more with them.
We already have a precise and accurate theory for protein folding. What we don’t have is the computational power to do true precise simulations at a scale and speed we’d like.
In many aspects a huge tangled barely documented code base written by inexperienced grad students of quantum shortcuts, err, perturbative methods isn’t that much more or less intelligible than an AI model learning those same methods.
What "precise and accurate theory for protein folding" exists?
Nobody has been able to demonstrate convincingly that any simulation or theory method can reliably predict the folding trajectory of anything but the simplest peptides.
> What "precise and accurate theory for protein folding" exists?
It’s called Quantum Mechanics.
> Nobody has been able to demonstrate convincingly that any simulation or theory method can reliably predict the folding trajectory of anything but the simplest peptides.
No we don’t have simplified models or specialized theories to reduce the computational complexity enough to efficiently solve the QM or even molecular dynamics systems needed to predict protein folding for more than the simplest peptides.
Granted, it’s common to mix up things and say that not having a computationally tractable models means we don’t have precise and accurate theory of PF. Something like [0] resulting in an accurate, precise, and fast theory of protein folding would be incredibly valuable. This however, may not be possible outside specific cases. Though I believe AlphaFold indicates otherwise as it appears life has evolved various building blocks which enable a simpler physics of PF tractable to evolutionary processes.
Quantum computing however could change that [1]. If practical QM is feasible that is, which it’s beginning to look more and more likely. Some say QC is already proven and just needs scaled up.
I don't think anybody is 100% certain that doing a full quantum simulation of a protein (in a box of water) would recapitulate the dynamics of protein folding. It seems like a totally reasonable claim, but one that could not really be evaluated.
If you have a paper that makes a strong argument around this claim, I'd love to see it. BTW- regarding folding funnels, I learned protein folding from Ken Dill as a grad student in biophysics at UCSF, and used to run MD simulations of nucleic acids and proteins. I don't think anybody in the field wants to waste the time worrying about running full quantum simulations of protein folding, it would be prohibitevly expensive even with far better QM simulators than we have now (IE, n squared or better).
Also the article you linked- they are trying to find the optimal structure (called fold by some in the field). That's not protein folding- it's ground state de novo structure prediction. Protein folding is the process by which an unfolded protein adopts the structured state, and most proteins don't actually adopt some single static structure but tend to interconvert between several different substructes that are all kinetically accessible.
> I don't think anybody is 100% certain that doing a full quantum simulation of a protein (in a box of water) would recapitulate the dynamics of protein folding.
True, until it's experimentally shown there's still some possibility QM wouldn't suffice. Though I've not read anything that'd give reason to believe QM couldn't capture the dynamic behavior of folding, unlike the uncertainty around dark matter or quantum supremacy or quantum gravity.
Though it might be practically impossible to setup a simulation using QM which could faithfully capture true protein folding. That seems more likely.
> It seems like a totally reasonable claim, but one that could not really be evaluated.
If quantum supremeacy holds, my hunch would be that it would be feasible to evaluate it one day.
The paper I linked was mostly to showcase that there seem to be approaches utilizing quantum computing to speed up solving QM simulations. We're still in the early days of quantum computing algorithms and it's unclear what's possible yet. Tackling a dynamic system like a unfolded protein folding is certainly a ways away though!
> Also the article you linked- they are trying to find the optimal structure (called fold by some in the field). That's not protein folding- it's ground state de novo structure prediction.
Thanks! I haven't worked on quantum chemistry for many years, and only tangentially on protein folding, so useful to know the terminology. The meta table states and that whole possibility of folding states / pathways / etc fascinates me as potentially being emergent property of protein folding physics and biology as we know it.
One one hand, maybe it's good to have better searchable records, even if it's hard to quantify the benefit.
On the other hand, now all your meetings produce reams of computer searchable records subject to discovery in civil and criminal litigation, possibly leading to far worse liability than would have been possible in a mostly email based business.
I doubt that, but even if you're right it doesn't change my point: if you're not willing to stop doing that, you'll be less productive than the firms that are willing to operate legally and ethically.
And if in some industry it's really not possible to do business without committing crimes, then let's reform the criminal code to something reasonable.
The problem is that the hype assumes that all of this is a baseline (or even below the baseline), while there are no signs that it can go much further in the near future – and in some cases, it's actually cutting-edge research. This leads to a pushback that may be disproportionate.
I'm sure there's many people out there who could say that they hardly use AI but that crypto has made them lots of money.
At the end of the day searching work documents and talking with computers is only desirable inasmuch as they are economically profitable. Crypto at the end of the day is responsible for a lot of people getting wealthy. Was a lot of this wealth obtained on sketchy grounds? probably, but the same could be said AI (for example, the recent sale of windsurf for an obscene amount of money).
Crypto is not creating anything. Its a scheme that is based on gamble.
Person A gets rich. Person B loses money. It does not really contribute to anything.
> is only desirable inasmuch as they are economically profitable.
The bug difference is that they are profitable because they create value, when cryptocurrencies are a zero sum game between participants. (It is in fact a negative-sum game, since some people are getting paid to make the thing work so that others can gamble on the system).
Alone language translation got so much better, voice syntesis, voice transcription.
All my meetings now are searchable and i can ask 'ai' to summarize my meetings in a relative accurate way impossible before that.
Alphafold made a breakthrough in protein folding.
Image and Video generation can now do unbelievable things.
Realtime voice communication with computer.
Our internal company search suddenly became usefull.
I have 0 use case for NFT and Crypto. I have tons of use case for ML.