Chemistry Nobel: Computational protein design and protein structure prediction • Hacker News Board

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

#301

Post by jltsiren » Thu, Oct 10, 2024, 12:05 AM UTC

a_bonobo wrote: post #295

jltsiren wrote: post #269

Earlier quoted context omitted.

> It also proved that deep learning models are a valid approach to bioinformatics A lot of bioinformatics tools using deep learning appeared around 2017-2018. But rather than being big breakthroughs like AlphaFold, most of them were just incremental improvements to various technical tasks in the middle of a pipeline.

and since a lot of those tools are incremental improvements they disappeared again, imho - what's the point for 2% higher accuracy when you need a GPU you don't have? Not many DL based tools I see these days regularly applied in genomics. Maybe: Tiara for 'high level' taxonomic classification, DeepVariant in some papers for SNP calling, that's about it? Some interesting gene prediction tools coming up like Tiberius.…

Most Oxford Nanopore basecallers use DL these days. And if you want a high quality de novo assembly, DL based methods are often used for error correction and final polishing.

There are a lot of differences between the cutting-edge methods that produce the best results, the established tools the average researcher is comfortable using, and whatever you are allowed to use in a clinical setting.

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

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Post by djtango » Thu, Oct 10, 2024, 1:15 AM UTC

concordDance wrote: post #263

chongli wrote: post #187

Earlier quoted context omitted.

Because having some degree of runway is almost always necessary but never sufficient. Thousands of Americans receive similar amounts of money from their parents in the form of inheritance of the family home and other major assets. Only one took windfall of that size and created Amazon.

The "necessary, but not sufficient" is unintuitive to most people. Billionaires who come from working class families are almost unheard of, but probably more than half the self made (for a definition, something like multiplied familial investments by at least 100x maybe?) billionaires come from upper middle class families. I wonder if they are actually more likely to come from upper middle class (where parents are hi…

Yes... Like Taylor Swift

To my mind, Joe Rogan is the most recent embodiment of the American dream which is why I think he is so popular

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

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Post by throwaway2037 » Thu, Oct 10, 2024, 1:18 AM UTC

nextworddev wrote: post #135

singularity2001 wrote: post #128

Earlier quoted context omitted.

whose father was one of the leading local industrialists (installing the first electric lighting for the 1885 Munich Oktoberfest)

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

About Warren Buffett, I was surprised to see his name here. Wiki tells me that his father, Howard Buffett, was:

    > four-term Republican United States Representative for the state of Nebraska

To me, that doesn't sound super impressive. Also:

    > After failing to secure a job in the family grocery business, he started a small stock brokerage firm.

Ok, that sounds less impressive. Further:

    > During his first term, when congressional salary was raised from $10,000

Oh wait. That is real money. 10k USD in 1943 is 180k today. Surely upper middle class by any measure.

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

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Post by throwawaymaths » Thu, Oct 10, 2024, 2:54 AM UTC

mhrmsn wrote: post #180

eig wrote: post #117

I think I disagree with most of the comments here stating it’s premature to give the Nobel to AlphaFold. I’m in biotech academia and it has changed things already. Yes the protein folding problem isn’t “solved” but no problem in biology ever is. Comparing to previous bio/chem Nobel winners like Crispr, touch receptors, quantum dots, click chemistry, I do think AlphaFold already has reached sufficient level of impact.

Crispr is widely used and there are even therapies approved based on it, you can actually buy TVs that use quantum dots and click chemistry has lots of applications (bioconjugation etc.), but I don't think we have seen that impact from AlphaFold yet. There's a lot of pharma companies and drug design startups that are actively trying to apply these methods, but I think the jury is still out for the impact it will fina…

What is the application for click chemistry again? Can you name a single drug that was medchemmed using click? I can't.

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

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Post by throwawaymaths » Thu, Oct 10, 2024, 2:57 AM UTC

lysozyme wrote: post #298

For those like myself who design proteins for a living, the open secret is that well before AlphaFold, it was pretty much possible to get a good-enough structure of any particular protein you really cared about (from say 2005) by other means, namely Baker’s Rosetta. I constantly use AlphaFold structures today [1]. And AlphaFold is fantastic. But it only replaces one small step in solving any real-world problem involv…

Forget Rosetta. Even installing that shit was hard, and running it on a sufficiently beefy machine was probably really not a thing in the late aughts. For protein design you mostly just need a quick and dirty estimate of what it looks like, and you have friend proteins that can be used to homology map, you could just use phyre/phyre2, which is an online threading model and be close enough to get work done. Upload the pdb, upload the sequence, bing bam boom.

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

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Post by hackernewds » Thu, Oct 10, 2024, 3:14 AM UTC

bonoboTP wrote: post #270

mk_stjames wrote: post #218

Earlier quoted context omitted.

I'm always interested in hearing about these people who go and get a PhD in an unrelated field to their original studies, often years after leaving university and working in an industry. Here it says Hasabis did an undergraduate degree in a computer science program, and them spent a decade working on computer games at studios, and then somehow just rocked up to a university and asked to do a PhD in neuroscience. I fe…

That may be more true in a super crowded and hot area, like AI now where reputable profs get dozens of PhD applicants per position, who all have already published relevant works in the field at top venues during their masters. In more chill fields where the waters are relatively calm, this may be less of an issue. But let's also consider the fact that Hassabis did his undergrad at the University of Cambridge, likely…

you assume likely with excellent results. perhaps his results weren't excellent?

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

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Post by hackernewds » Thu, Oct 10, 2024, 3:15 AM UTC

lysozyme wrote: post #298

For those like myself who design proteins for a living, the open secret is that well before AlphaFold, it was pretty much possible to get a good-enough structure of any particular protein you really cared about (from say 2005) by other means, namely Baker’s Rosetta. I constantly use AlphaFold structures today [1]. And AlphaFold is fantastic. But it only replaces one small step in solving any real-world problem involv…

Rosetta was clunky and not even David Baker would endorse it

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

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Post by hackernewds » Thu, Oct 10, 2024, 3:16 AM UTC

paulwetzel wrote: post #4

While I am skeptical about yesterdays award in physics, these are totally deserved and spot on. There are few approaches that will accelerate the field of drug development and chemistry as a whole in a way that the works of these three people will. Congratulations!

Well deserved! My only qualm is it should've been awarded to the team, vs individuals

It needed Oriol as well doing IC work

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

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Post by suriya-ganesh » Thu, Oct 10, 2024, 3:30 AM UTC

hackernewds wrote: post #306

bonoboTP wrote: post #270

Earlier quoted context omitted.

That may be more true in a super crowded and hot area, like AI now where reputable profs get dozens of PhD applicants per position, who all have already published relevant works in the field at top venues during their masters. In more chill fields where the waters are relatively calm, this may be less of an issue. But let's also consider the fact that Hassabis did his undergrad at the University of Cambridge, likely…

you assume likely with excellent results. perhaps his results weren't excellent?

likely because hassabis was a child prodigy. Was a chess master at 13. Lead Cambridge chess team. its not surmise to assume that demis had impeccable school record

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

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Post by theGnuMe » Thu, Oct 10, 2024, 3:34 AM UTC

patall wrote: post #241

theGnuMe wrote: post #209

Earlier quoted context omitted.

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

I do not criticize them for having FOMO. But I have my doubts when it is the 60-year-olds that are the most enthusiastic about something new (as long as it is not a new ABBA album), given the number of grifters out there. And there would have been many others that also deserve a Nobel, those three could easily have waited another 20 years. If it really was those that had the highest impact the last year who won the p…

Right but this is a paradigm shift. If anything the 60 year-olds dumped on AI. Statisticians dumped on AI. Cybernetics/engineers all dumped on it. Just like everyone dumped on mRNA vaccines. I do agree with you about GLP-1 though that's legit as is the HIV vaccine.

But still the way forward is computational thinking that is very clear.