AlphaFold 3 predicts the structure and interactions of life's molecules • Hacker News Board

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#291

Post by pas » Wed, May 08, 2024, 8:25 PM UTC

chasd00 wrote: post #270

ak_111 wrote: post #252

Earlier quoted context omitted.

Discovering underlying principles and predicting outcomes is two sides of the same coin in that there is no way to confirm you have discovered underlying principles unless they have some predictive power. Some had tried to come up with other criteria to confirm you have discovered an underlying principle without predictive power, such as on aesthetics - but this is seen by the majority of scientists as basically a co…

If all you can do is predict an outcome without being able to explain how then what have you really discovered? Asking someone to just believe you can predict outcomes without any reasoning as to how, even if you're always right, sounds like the concept of faith in religion.

it's still an extremely valuable tool. just as we see in mathematics, closed forms (and short and elegant proofs) are much coveted luxury items.

for many basic/fundamental mathematical objects we don't (yet) have simple mechanistic ways to compute them.

so if a probabilistic model spits out something very useful, we can slap a nice label on it and call it a day. that's how engineering works anyway. and then hopefully someday someone will be able to derive that result from "first principles" .. maybe it'll be even more funky/crazy/interesting ... just like mathematics arguably became more exciting by the fact that someone noticed that many things are not provable/constructable without an explicit Axiom of Choice.

https://en.wikipedia.org/wiki/Nonelementary_integral#Example...

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#292

Post by d_silin » Wed, May 08, 2024, 8:28 PM UTC

mathgradthrow wrote: post #124

_yb2s wrote: post #120

Earlier quoted context omitted.

It means we now have an accurate surrogate model or "digital twin" that can be experimented on almost instantaneously. So we can massively accelerate the traditional process of developing mechanistic understanding through experiment, while also immediately be able to benefit from the ability to make accurate predictions, even without needing understanding. In reality, science has already pretty much gone this way lon…

instead of "in mice", we'll be able to say "in the cloud"

"in silico"

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#293

Post by thfuran » Wed, May 08, 2024, 8:29 PM UTC

pas wrote: post #291

chasd00 wrote: post #270

Earlier quoted context omitted.

If all you can do is predict an outcome without being able to explain how then what have you really discovered? Asking someone to just believe you can predict outcomes without any reasoning as to how, even if you're always right, sounds like the concept of faith in religion.

it's still an extremely valuable tool. just as we see in mathematics, closed forms (and short and elegant proofs) are much coveted luxury items. for many basic/fundamental mathematical objects we don't (yet) have simple mechanistic ways to compute them. so if a probabilistic model spits out something very useful, we can slap a nice label on it and call it a day. that's how engineering works anyway. and then hopefully…

>closed forms (and short and elegant proofs) are much coveted luxury items.

Yes, but we're taking about roughly the opposite of a proof

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#294

Post by jltsiren » Wed, May 08, 2024, 8:34 PM UTC

strogonoff wrote: post #238

jprete wrote: post #194

Earlier quoted context omitted.

The goal of science has always been to discover underlying principles and not merely to predict the outcome of experiments. I don't see any way to classify an opaque ML model as a scientific artifact since by definition it can't reveal the underlying principles. Maybe one could claim the ML model itself is the scientist and everyone else is just feeding it data. I doubt human scientists would be comfortable with that…

Can underlying principles be discovered using the framework of scientific method? The primary goal of models and theories it develops is to support more experiments and eventually be disproven. If no model can be correct, complete and provable in finite time, then a theory about underlying principles that claims completeness would have to be unfalsifiable. This is reasonable in context of philosophy, but not in natur…

I don't find that argument convincing.

People clearly have been able to discover many underlying principles using the scientific method. Then they have been able to explain and predict many complex phenomena using the discovered principles, and create even more complex phenomena based on that. Complex phenomena such as the technology we are using for this discussion.

Words dont have any inherent meaning, just the meaning they gain from usage. The entire concept of truth is an artifact of just some model (language) we came up with previously—a model which, per above, is probably incomplete/incorrect. The kind of absolute truth you are talking about may make sense when discussing philosophy or religion. Then there is another idea of truth more appropriate for talking about the empirical world. Less absolute, less immutable, less certain, but more practical.

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#295

Post by jcims » Wed, May 08, 2024, 8:44 PM UTC

chasd00 wrote: post #270

ak_111 wrote: post #252

Earlier quoted context omitted.

Discovering underlying principles and predicting outcomes is two sides of the same coin in that there is no way to confirm you have discovered underlying principles unless they have some predictive power. Some had tried to come up with other criteria to confirm you have discovered an underlying principle without predictive power, such as on aesthetics - but this is seen by the majority of scientists as basically a co…

If all you can do is predict an outcome without being able to explain how then what have you really discovered? Asking someone to just believe you can predict outcomes without any reasoning as to how, even if you're always right, sounds like the concept of faith in religion.

Isn’t that basically true of most of the fundamental laws of physics? There’s a lot we don’t understand about gravity, space, time, energy, etc., and yet we compose our observations of how they behave into very useful tools.

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#296

Post by variadix » Wed, May 08, 2024, 8:50 PM UTC

Invictus0 wrote: post #265

variadix wrote: post #199

Earlier quoted context omitted.

There is an issue scientifically. I think this point was expressed by Feynman: the goal of scientific theories isn’t just to make better predictions, it’s to inform us about how and why the world works. Many ancient civilizations could accurately predict the position of celestial bodies with calendars derived from observations of their period, but it wasn’t until Copernicus proposed the heliocentric model and Galileo…

But we do know why, it's just not simple. The atoms interact with one another because of a variety of fundamental forces, but since there can be hundreds of thousands of atoms in a single protein, it's plainly beyond human comprehension to explain why it folds the way it does, one fundamental force interaction at a time.

Fair. I guess the interesting thing for protein folding research then is that there appears to be a way to approximate/simplify the calculations required to predict folding patterns that doesn’t require the precision of existing folding models and software. In essence, AlphaFold is an existence proof that there should be a way to model protein folding more efficiently.

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#297

Post by j-wags » Wed, May 08, 2024, 8:53 PM UTC

iknowstuff wrote: post #234

firefoxbrower wrote: post #227

Earlier quoted context omitted.

Late-stage capitalism didn't bring us AlphaFold, scientists did, late-stage capitalism just brought us Alphabet swooping in at literally the last minute. Socialize the innovation because that requires potential losses, privatize the profits, basically. It's reminiscent of "Heroes of CRISPR," where Doudna and Charpentier are supposedly just some middle-men, because stepping in at the last minute with more funding is r…

Why haven't the academics created a non profit foundation with open source models like this then? If alphabet doesnt provide much, then they will be supplanted by non profits. I see nothing broken here.

I work at Open Force Field [1] which is the kind of nonprofit that I think you're talking about. Our sister project, OpenFold [2], is working on open source versions of AlphaFold.

We're making good progress but it's difficult to interface with fundamentally different organizational models between academia and industry. I'm hoping that this model will become normalized in the future. But it takes serious leaps of faith from all involved (professors, industry leaders, grant agencies, and - if I can flatter myself - early career scientists) to leave the "safe route" in their organizations and try something like this.

[1] https://openforcefield.org/ [2] https://openfold.io/

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#298

Post by variadix » Wed, May 08, 2024, 8:57 PM UTC

interroboink wrote: post #243

variadix wrote: post #199

Earlier quoted context omitted.

There is an issue scientifically. I think this point was expressed by Feynman: the goal of scientific theories isn’t just to make better predictions, it’s to inform us about how and why the world works. Many ancient civilizations could accurately predict the position of celestial bodies with calendars derived from observations of their period, but it wasn’t until Copernicus proposed the heliocentric model and Galileo…

I agree the how/why is the main driving goal. That's kinda why I feel like this is not depressiong news — there's a new frontier to discover and attempt to explain. Scientists love that stuff (: Knowing how to predict the motion of planets but without having an underlying explanation encourages scientists to develop their theories. Now, once more, we know how to predict something (protein folding) but without an unde…

I was mainly responding to the claim that these black boxes produce a hypothesis that is useful as a basis for scientific theories. I don’t think it does, because it offers no explanation as to the how and why, which is as we agree the primary goal. It doesn’t provide a hypothesis per se, just a prediction, which is useful technologically and should indicate that there is more to be discovered (see my response to the sibling reply) scientifically but offers no motivating explanation.

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#299

Post by dumpsterdiver » Wed, May 08, 2024, 8:59 PM UTC

chasd00 wrote: post #270

ak_111 wrote: post #252

Earlier quoted context omitted.

Discovering underlying principles and predicting outcomes is two sides of the same coin in that there is no way to confirm you have discovered underlying principles unless they have some predictive power. Some had tried to come up with other criteria to confirm you have discovered an underlying principle without predictive power, such as on aesthetics - but this is seen by the majority of scientists as basically a co…

If all you can do is predict an outcome without being able to explain how then what have you really discovered? Asking someone to just believe you can predict outcomes without any reasoning as to how, even if you're always right, sounds like the concept of faith in religion.

> what have you really discovered?

You’ve discovered magic.

When you read about a wizard using magic to lay waste to invading armies, how much value would you guess the armies place in whether or not the wizard truly understands the magic being used against them?

Probably none. Because the fact that the wizard doesn’t fully understand why magic works does not prevent the wizard from using it to hand invaders their asses. Science is very much the same - our own wizards used medicine that they did not understand to destroy invading hordes of bacteria.

Re: AlphaFold 3 predicts the structure and interactions of life's molecules

#300

Post by gradus_ad » Wed, May 08, 2024, 9:07 PM UTC

jprete wrote: post #194

dekhn wrote: post #93

Earlier quoted context omitted.

If you're a scientist who works in protein folding (or one of those other areas) and strongly believe that science's goal is to produce falsifiable hypotheses, these new approaches will be extremely depressing, especially if you aren't proficient enough with ML to reproduce this work in your own hands. If you're a scientist who accepts that probabilist models beat interpretable ones (articulated well here: https://no…

The goal of science has always been to discover underlying principles and not merely to predict the outcome of experiments. I don't see any way to classify an opaque ML model as a scientific artifact since by definition it can't reveal the underlying principles. Maybe one could claim the ML model itself is the scientist and everyone else is just feeding it data. I doubt human scientists would be comfortable with that…

That ship sailed with Quantum physics. Nearly perfect at prediction, very poor at giving us a concrete understanding of what it all means.

This has happened before. Newtonian mechanics was incomprehensible spooky action at a distance, but Einstein clarified gravity as the bending of spacetime.