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

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

#361
post #246

Earlier quoted context omitted.

Abstraction isn't the silver bullet. Not everything is abstractable. "This program generates the most likely outputs" isn't a scientific explanation, it's teleology.

"this tool works better than my intuition" absolutely is science. "be quiet and calculate" is a well worn mantra in physics is it not?

“calculate” in that phrase, refers to doing the math, and the understanding that that entails, not pressing the “=“ button on a calculator.

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

#362

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.

The how is actually just further hypotheses. It's turtles all the way down: There is a car. We think it drives by burning petrol somehow. How do we test this? We take petrol away and it stops driving. Ok, so we know it has something to do with petrol. How does it burning the petrol make it drive? We think it is caused by the burned petrol pushing the cylinders, which are attached to the wheels through some gearing. H…

>There is a car. We think it drives by burning petrol somehow. How do we test this? We take petrol away and it stops driving.

You discovered a principle.

Better example:

There is a car. We don’t know how it drives. We turn the blinkers on and off. It still drives. Driving is useful. I drive it to the store

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

#363
post #93

Stepping back, the high-order bit here is an ML method is beating physically-based methods for accurately predicting the world. What happens when the best methods for computational fluid dynamics, molecular dynamics, nuclear physics are all uninterpretable ML models? Does this decouple progress from our current understanding of the scientific process - moving to better and better models of the world without human-int…

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…

> If you're the sort of person who believes that human brains are capable of understanding the "why" of how things work in all its true detail, you'll find this an interesting challenge- can we actually interpret these models, or are human brains too feeble to understand complex systems without sophisticated models?

I think chess engines, weirdly enough, have disabused me of this notion.

There are lots of factors a human considers when looking at a board. Piece activity. Bishop and knight imbalances. King safety. Open and semi-open file control. Tempo. And on and on.

But all of them are just convenient shortcuts that allow us to substitute reasonable guesses for what really matters: exhaustively calculating a winning line through to the end. “Positional play” is a model that only matters when you can’t calculate trillions of lines thirty moves deep, and it’s infinitely more important that a move survives your opponent’s best possible responses than it is to satisfy some cohesive higher level principle.

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

#364
post #257
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…

Kepler famously compiled troves of data on the night sky, and just fitted some functions to them. He could not explain why but he could say what. Was he not a scientist?

He might not have been able to explain why _but_ I'd bet anything he would have wanted to if he could.

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

#365
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…

> If you're the sort of person who believes that human brains are capable of understanding the "why" of how things work in all its true detail, you'll find this an interesting challenge- can we actually interpret these models, or are human brains too feeble to understand complex systems without sophisticated models? I think chess engines, weirdly enough, have disabused me of this notion. There are lots of factors a h…

Chess engines actually do both now. They have ML models to evaluate positions, essentially a much more advanced version of your positional description, and deep calculations.

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

#366
post #200

Earlier quoted context omitted.

That's the aspirational goal. And I would say that it's a bit of an inflexible one- for example, if we had an ML that could generate molecules that cure diseases that would pass FDA approval, I wouldn't really care if scientists couldn't explain the underlying principles. But I'm an ex-scientist who is now an engineer, because I care more about tools that produce useful predictions than understanding underlying princ…

> if we had an ML that could generate molecules that cure diseases that would pass FDA approval, I wouldn't really care if scientists couldn't explain the underlying principles It’s actually required as part of the submission for FDA approval that you posit a specific Mechanism of Action for why your drug works the way it does. You can’t get approval without it

A substantial proportion of FDA-approved drugs have an unknown mechanism of action - we can handwave about protein interactions, but we have no useful insight into how they actually work. Drug discovery is bureaucratically rigid, but scientifically haphazard.

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

#367

Earlier quoted context omitted.

> If you're the sort of person who believes that human brains are capable of understanding the "why" of how things work in all its true detail, you'll find this an interesting challenge- can we actually interpret these models, or are human brains too feeble to understand complex systems without sophisticated models? I think chess engines, weirdly enough, have disabused me of this notion. There are lots of factors a h…

Chess engines actually do both now. They have ML models to evaluate positions, essentially a much more advanced version of your positional description, and deep calculations.

That might be the best we can practically achieve with technology, but the point stands. If positional evaluation says one thing but an exhaustive analysis of lines finds a solution 60 moves deep, that one is going to win.

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

#368
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…

What always struck me about Chomskyists is that they chose a notion of interpretable model that required unrealistic amounts of working interpretation. So Chomsky grammars have significant polynomial memory and computational costs for grammars as they approach something resembling human grammar. And you say, ok, the human brain can handle much more computation than that, and that's fine. But (for example) context-fre…

There is a ballmer peak for pontificating.

As an aside but relevant to your point, my entire introduction to DNA and protein analysis was based on Chomsky grammars. My undergrad thesis advisor David Haussler handed me a copy of an article by David Searls "The Linguistics of DNA" (https://www.scribd.com/document/461974005/The-Linguistics-of...) . At the time, Haussler was in the middle of applying HMMs and other probabilistic graphical models to sequence analysis, and I knew all about DNA as a molecule, but not how to analyze it.

Searls paper basically walks through Chomsky's hierarchy, and how to apply it, using linguistic techniques to "parse" DNA. It was mind-bending and mind-expanding for me (it takes me a long time to read papers, for example I think I read this paper over several months, learning to deal with parsing along the way). To this day I am astounded at how much those approaches (linguistics, parsing, and grammars) have evolved- and yet not much has changed! People were talking about generative models in the 90s (and earlier) in much the same way we treat LLMs today. While much of Chomsky's thinking on how to make real-world language models isn't particuarly relevant, we still are very deeply dependent on his ideas for grammar...

Anyway, back to your point. While CFGs may be O(n*3) I would say that there is a implicit, latent O(n) parseable grammar underlying human linguistics, and our brains can map that latent space to its own internal representation in O(1) time, where the n roughly correlates to the complexity of the idea being transferred. It does not seem even remotely surprising that we can make multi-language models that develop their own compact internal representation that is presumably equidistant from each source language.

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

#369

Earlier quoted context omitted.

"There is no 'truth' that we can grasp in parts but not entirely." The value of pi is a simple counterexample.

We can predict the digits of pi with a formula, to me that counts as grasping it

For those who aren't aware: https://en.wikipedia.org/wiki/Bellard%27s_formula (yes, that Fabrice: https://en.wikipedia.org/wiki/Fabrice_Bellard)

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

#370
post #93

Stepping back, the high-order bit here is an ML method is beating physically-based methods for accurately predicting the world. What happens when the best methods for computational fluid dynamics, molecular dynamics, nuclear physics are all uninterpretable ML models? Does this decouple progress from our current understanding of the scientific process - moving to better and better models of the world without human-int…

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…

Do you think a model will also be able to truly comprehend everything too ?
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