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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

#211

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…

I think it likely that instead of replacing existing methods, we will see a fusion. Or rather, many different kinds of fusions - depending on the exact needs of the problems at hand (or in science, the current boundary of knowledge). If nothing else then to provide appropriate/desirable level of explainability, correctness etc. Hypothetically the combination will also have better predictive performance and be more data efficient - but it remains to be seen how well this plays out in practice. The field of "physics informed machine learning" is all about this.

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

#212
post #24

Earlier quoted context omitted.

Also no commercial use, from the paper: > AlphaFold 3 will be available as a non-commercial usage only server at https://www.alphafoldserver.com , with restrictions on allowed ligands and covalent modifications. Pseudocode describing the algorithms is available in the Supplementary Information. Code is not provided.

What's the point in that that - I mean who does non-commercial drug research?

Public universities?

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

#213

Earlier quoted context omitted.

That's pretty good. Based on the previous performance improvements of Alpha-- models, it'll be nearing 100% in the next couple of years.

Just "Alpha-- models" in general?? That's not a remotely reasonable way to reason about it. Even if it were, why should it stop DeepMind from clearly communicating accuracy?

The way I think about this (specifically, deepmind not publishing their code or sharing their exact experimental results): advanced science is a game played by the most sophisticated actors in the world. Demis is one of those actors, and he plays the games those actors play better than anybody else I've ever seen. Those actors don't care much about the details of any specific system's accuracy: they care to know that it's possible to do this, and some general numbers about how well it works, and some hints what approaches they should take. And Nature, like other top journals, is more than willing to publish articles like this because they know it stimulates the most competitive players to bring their best games.

(I'm not defending this approach, just making an observation)

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

#214

Earlier quoted context omitted.

It makes me think about how Einstein was famous for making falsifiable real-world predictions to accompany his theoretical work. And, sometimes it took years for proper experiments to be run (such as measuring a solar eclipse during the breakout of a world war). Perhaps the opportunity here is to provide a quicker feedback loop for theory about predictions in the real world. Almost like unit tests.

Agreed. At the very least, models of this nature let us iterate/filter our theories a little bit more quickly.

The model isn't reality. A theory that disagrees with the model but agrees with reality shouldn't be filtered, but in this process it will be.

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

#215

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…

Perhaps for understanding the structure itself, but having the structure available allows us to focus on a coarser level. We also don't want to use quantum mechanics to understand the everyday world, and that's why we have classic mechanics etc.

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

#216

As a software engineer, I kind of feel uncomfortable about this new model. It outperforms Alphafold 2 at ligand binding, but Alphafold 2 also had some more hardcoded and interpretable structural reasoning baked into the model architecture. There's so many things you can incorporate into a protein folding model such as structural constraints, rotational equivariance, etc, etc This new model simple does away with some…

Consider that humans also learn from other humans, and sometimes surpass their teachers.

A bit more comfortable?

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

#217
post #173
post #110

Earlier quoted context omitted.

the R&D of all major pharma is currently using AlphaFold predictions when they don't have experimentally determined structures. I cannot share further details but the results suggest that we will see future pharmaceuticals based on AF predictions. The important thing to recognize is that protein structures are primarily hypothesis-generation machines and tools to stimulate ideas, rather that direct targets of computa…

Sure. If/when we see anything practical, that’ll be the right moment to pay attention. This is much like “quantum computing” where everyone who doesn’t know what it is is excited for some reason, and those that do know can’t even articulate any practical applications

Feynman already articulated the one practical application for quantum computing: using it to simulate complex systems (https://www.optica-opn.org/home/articles/on/volume_11/issue_... and https://calteches.library.caltech.edu/1976/ and https://s2.smu.edu/~mitch/class/5395/papers/feynman-quantum-...

These approaches are now being explored but I haven't seen any smoking guns showing a QC-based simulation exceeding the accuracy of a classical computer for a reasonable investment.

Folks have suggested other areas, such as logistics, where finding small improvements to the best approximations might give a company a small edge, and crypto-breaking, but there has been not that much progress in this area, and the approximate methods have been improving rapidly.

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

#218

Important caveat: it's only about 70% accurate. Why doesn't the press release say this explicitly? It seems intentionally misleading to only report accuracy relative to existing methods, which apparently are just not so good (30%, 50% in various settings). https://www.fastcompany.com/91120456/deepmind-alphafold-3-dn...

IIRC the next best models all have all been using AlphaFold 2's methodology, so that's still a massive improvement.

Edit: I see now that you're probably objecting to the headline that got edited on HN.

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

#219
I wonder in the not too distant future if these AI predictions could be explained back into “humanized” understanding. Much like ChatGPT can simplify complex topics … cold the model in the future provide feedback to researchers why it is making this prediction?

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

#220

As a software engineer, I kind of feel uncomfortable about this new model. It outperforms Alphafold 2 at ligand binding, but Alphafold 2 also had some more hardcoded and interpretable structural reasoning baked into the model architecture. There's so many things you can incorporate into a protein folding model such as structural constraints, rotational equivariance, etc, etc This new model simple does away with some…

> Makes me feel a bit uncomfortable.

Why? Do compilers which can't bootstrap themselves also make you uncomfortable due to dependencies on pre-built artifacts? I'm not saying you're unjustified to feel that way, but sometimes more abstracted systems are quicker to build and may have better performance than those built from the ground up. Selecting which one is better depends on your constraints and taste

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