AlphaFold Protein Structure Database • Hacker News Board

Re: AlphaFold Protein Structure Database

#31

Post by narrator » Thu, Jul 22, 2021, 6:30 PM UTC

narrator wrote: post #27

drcode wrote: post #24

Earlier quoted context omitted.

...and many doctors will use it to attach pharmaceuticals to receptor sites of particular cancers.

I'm thinking that the problem is is that it is much harder to develop drugs that only kill cancers very efficiently and don't harm the rest of the body than to tweak viruses that just have to keep the person alive long enough to spread the virus.

The crazy part is a bioweapons program is really cheap compared to a nuclear weapons program, and now with these new tools it's even cheaper. Before, it was vastly more expensive to do the cycle of creating a new viral protein and testing a bioweapon on human cell culture. Now that process is speeded up millions of times with this technology because that can all take place inside a computer.

This is similar to the change with drone weaponry. Before, you had to have large cruise missiles to get pinpoint strikes. Now small countries like Azerbaijan can buy a whole fleet of drone weapons and get the benefits of having a modern air force with pinpoint strikes and even stealth for vastly less money.

Re: AlphaFold Protein Structure Database

#32

Post by ramraj07 » Thu, Jul 22, 2021, 6:34 PM UTC

vmception wrote: post #23

nharada wrote: post #11

From the abstract[1]: > After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally-determined structure. Here we dramatically expand structural coverage by applying the state-of-the-art machine learning method, AlphaFold2, at scale to almost the entire human proteome (98.5% of human proteins). [1] https://www.nature.com/articles/s41586-021-03828-1

Basically they are saying that decades of distributed protein folding was useless and everyone would have had more utility mining cryptocurrency if it existed several years earlier But at least it inspired someone to make and release this

I don't know if you know, but doctors spent 1,300 YEARS using the wrong anatomy book. A few years and compute time isnt the end of the world. I'm sure oracle's DB2 test suite has burned more carbon than protein folding labs have.

Re: AlphaFold Protein Structure Database

#33

Post by ramraj07 » Thu, Jul 22, 2021, 6:36 PM UTC

Ovah wrote: post #21

Interesting that they're porting it to other organisms. Different organisms have variations in ribosomes, post translational modifications and even tRNA repertoire. So it's not a guarantee that two identical DNA sequences will give identical proteins in two different organisms.

??? Unless you jump from eukaryotes to archea these are not real concerns. Most PTM markers are very conserved.

Re: AlphaFold Protein Structure Database

#34

Post by ramraj07 » Thu, Jul 22, 2021, 6:38 PM UTC

As an ex biomedical researcher I was trying to think what protein I should enter and see, and couldn't come up with a protein that I know of, that didn't have a structure already (at least a crude one). That is, we roughly know how most known important proteins look like. This is an amazing tool, and will he indispensable in labs (I'll expect any lab to use this site at least once a year?) But it's not as transformative as some might think.

Re: AlphaFold Protein Structure Database

#35

Post by dekhn » Thu, Jul 22, 2021, 6:47 PM UTC

vmception wrote: post #23

nharada wrote: post #11

From the abstract[1]: > After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally-determined structure. Here we dramatically expand structural coverage by applying the state-of-the-art machine learning method, AlphaFold2, at scale to almost the entire human proteome (98.5% of human proteins). [1] https://www.nature.com/articles/s41586-021-03828-1

Basically they are saying that decades of distributed protein folding was useless and everyone would have had more utility mining cryptocurrency if it existed several years earlier But at least it inspired someone to make and release this

you're conflating two different disciplines: distributed protein folding studies the biophysical process of proteins folding over time, while protein structure prediction makes a static single predict of what is believed to be the final structure adopted by the protein in the folding process.

I think many people believe that given infinite computer time the protein folding simulations would produce the same output as the static prediction (modulo a number of complex details) but use far, far more computer time to get there.

The fundamental observation from the DM AF2 paper that I've been able to glean (which I kind of sort of already believed) is that careful multiple sequence alignments of 30-100 evolutionarily related proteins is enough to produce coarse distance constraints that can be used to guide a structure prediction to a good answer quickly. And that depended on new ML technology that didn't exist before.

Re: AlphaFold Protein Structure Database

#36

Post by amelius » Thu, Jul 22, 2021, 6:49 PM UTC

ramraj07 wrote: post #34

As an ex biomedical researcher I was trying to think what protein I should enter and see, and couldn't come up with a protein that I know of, that didn't have a structure already (at least a crude one). That is, we roughly know how most known important proteins look like. This is an amazing tool, and will he indispensable in labs (I'll expect any lab to use this site at least once a year?) But it's not as transformat…

https://www.embl.org/news/science/alphafold-potential-impact...

> A discussion of the applications that AlphaFold DB may enable and the possible impact of the resource on science and society

Re: AlphaFold Protein Structure Database

#37

Post by vmception » Thu, Jul 22, 2021, 6:50 PM UTC

dekhn wrote: post #35

vmception wrote: post #23

Earlier quoted context omitted.

Basically they are saying that decades of distributed protein folding was useless and everyone would have had more utility mining cryptocurrency if it existed several years earlier But at least it inspired someone to make and release this

you're conflating two different disciplines: distributed protein folding studies the biophysical process of proteins folding over time, while protein structure prediction makes a static single predict of what is believed to be the final structure adopted by the protein in the folding process. I think many people believe that given infinite computer time the protein folding simulations would produce the same output as…

thanks for that explanation!

Re: AlphaFold Protein Structure Database

#38

Post by lumost » Thu, Jul 22, 2021, 6:58 PM UTC

I used to do some RNA molecular dynamics simulations in college which were both computationally expensive and difficult to replicate. Having the ability to reasonably predict protein structure is an incredible scientific achievement - however I am curious if anyone here who is better informed has takes on the following.

1. How likely is it that alphafold learned to accurately predict protein structure in the narrow domain of proteins that have been experimentally synthesized and whose structure has been measured? in other words will AlphaFold's results generalize to proteins which cannot yet be synthesized in the laboratory.

2. If Alphafold's accuracy holds, what type of commercial applications does this open up?

Re: AlphaFold Protein Structure Database

#39

Post by ravila4 » Thu, Jul 22, 2021, 7:16 PM UTC

narrator wrote: post #22

Gain of function researchers working for the world's militaries will use this research to figure out how to get viruses to attach to receptor sites peculiar to particular races. The people developing the antivirals will have a lot harder time countering these weapons because making antivirals that aren't poisonous in some weird way is a much harder job. If this is not the case, please let me know why, it will really…

1. Gain of function is not as easy as you think. 2. Such bio-weapons are not likely because any virus released in the wild will mutate over time, and also because you cannot target "races" in the way you describe. Phenotypic traits span across geographical borders, and any attempt to do such a thing is likely to backfire.

Re: AlphaFold Protein Structure Database

#40

Post by culopatin » Thu, Jul 22, 2021, 7:16 PM UTC

I happen to be working on a database for folds as well. But RNA folds not protein folds. I’m not a bio guy but my gf is and if I understand correctly this is not the same. I hope they are different because it would suck to be me lol.

This is my first big boy project and I’m driving solo so it takes me a while to make any progress. But at least now I have this db and genbank to model after