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Chemistry Nobel: Computational protein design and protein structure prediction

nobelprize.org

201–210 of 343 posts

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#201
post #84

Great achievement, although I think it's interesting that this Nobel prize was awarded so early, with "the greatest benefit on mankind" still outstanding. Are there already any clinically approved drugs based on AI out there I might have missed? In comparison, the one for lithium batteries was awarded in 2019, over 30 years after the original research, when probably more than half of the world's population already us…

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Re: Chemistry Nobel: Computational protein design and protein structure prediction

#202
post #153

I wasn't expecting to see David Baker in the list (just Demis and John). But I'm really glad to see it... David is a great guy. At CASP (the biannual protein structure prediction competition) around 2000, I sat down with David and told him that eventually machine learning would supplant humans at structure prediction (at the time Rosetta was already the leading structure prediction/design tool, but was filled with a…

They had to put David Baker on here, his work on protein design if nothing else was ground breaking. I've expected him to win it at some point in a, it's not a matter of if but of when.

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#203
post #97

> Oppenheimer was nominated for the Nobel Prize for Physics three times[...] pondered why he was never bestowed the honor. > “To understand this [...] you have to first examine the man’s academic life before and after the war.” Quote from: https://discover.lanl.gov/news/0609-oppie-nobel-prize/ Not anymore. You're not required to know or have studied Chemistry to get a Nobel in Chemistry.

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Re: Chemistry Nobel: Computational protein design and protein structure prediction

#205

Earlier quoted context omitted.

In both academic and industrial settings, I've seen an initial spark of hope about AlphaFold's utility being replaced with a resignation that it's cool, but not really useful. Yet in both settings it continued as a playing card for generating interest. There's an on-point blog-post "AI and Biology" ( https://www.science.org/content/blog-post/ai-and-biology ) which illustrates why AlphaFold's real breakthrough is not…

That article explains why AI might not work so well further down the line biology discoveries, but I still think alphafold can really help with the development of small molecule therapies that bind to particular known targets and not to others, etc.

The thing with available ligand + protein recorded structures is that they are much, much more sparse than available protein structures themselves (which are already kinda sparse, but good enough to allow AlphaFold). Some of the commonly-used datasets for benchmarking structure-based affinity models are so biased you can get a decent AUC by only looking at the target or ligand in isolation (lol).

Docking ligands doesn't make for particularly great structures, and snapshot structures really miss out on the important dynamics.

So it's hard for me to imagine how alphafold can help with small molecule development (alphafold2 doesn't even know what small molecules are). I agree it totally sounds plausible in principle, I've been in a team where such an idea was pushed before it flopped, but in practice I feel there's much less use to extract from there than one might think.

EDIT: To not be so purely negative: I'm sure real use can be found in tinkering with AlphaFold. But I really don't think it has or will become a big deal in small drug discovery workflows. My PoV is at least somewhat educated on the matter, but of course it does not reflect the breadth of what people are doing out there.

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#206
post #70

Earlier quoted context omitted.

doesn't beat that patent clerk guy

The patent clerk guy was almost done with his PhD when he became a patent clerk. Not quite comparable.

Uh. Demis finished his PhD...

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#207

Earlier quoted context omitted.

It’s fascinating how the affluent backgrounds of many famous scientists and entrepreneurs are downplayed. Eg Warren Buffet, Jeff Bezos, etc

If you gave the $300,000 Bezos got from his father to 10,000 random Americans in 1994, none of them would have created a company the equivalent of Amazon's scale.

That may be true, but I don't think that's really the crux of the argument. This article talks about how Amazon was initially funded by Bezos' family members: https://luxurylaunches.com/celebrities/jeff-bezos-parents-in.... The bigger point is that relatively very few parents (like a couple percent maybe?) would be in a position to give their kid $250k to start a new venture, and it's not that surprising that the most financially successful people in the world needed both: intrinsic talent and drive, and a huge amount of support from their birth circumstances.

The way I like to put it is that both of the following are true:

1. Bezos is uniquely talented and driven, and his success depended on that

2. Bezos' success also depended on him having an uncommon level of access to capital at a young age.

The reason I like to say "both of these are true" is that so often today I see "sides" that try to argue that only one is true, e.g. libertarian-leaning folks (especially in the US) arguing that everything is a pure meritocracy, and on the other side that these phenomenally successful people just inherited their situation (e.g. "Elon Musk is only successful because his dad owned an emerald mine")

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#209
post #114
post #89

I think it's still too early to know if AlphaFold is a massively overfitted statistical model that will utterly fail on novel structures.

The prize winners are ultimately selected by a group of mid-age to old professors. And to tell the truth (I work at a research institute in Stockholm), some of the old folks seem to have huge FOMO. They know that they cannot keep up themselves, they have no idea (and no way of finding out) who is actually good and who is just pretending, which leads to recruitment of an 'interesting' bunch of young group leaders. Som…

I dunno, you should have AI FOMO. Or at least start focusing on computational thinking.

Re: Chemistry Nobel: Computational protein design and protein structure prediction

#210

Well deserved! Especially for Alphafold. It is the most impactful invention in structural biology this century along with Cryo-EM.

It doesn't deserve a Chemistry Nobel prize. It deserves a prize about computers.

So the Nobel commite was wrong to decide this because you think otherwise?

Interesting. Any more indepth analys about this?

Btw. you don't just build AlphaFold by doing only 'computers'. Take a look at any good docmentary about it and you will see that they do discuss chemistry on a deep level

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