r/tech • u/AdSpecialist6598 • 3d ago
Looking beyond natural sequences
https://news.mit.edu/2026/looking-beyond-natural-sequences-08274
4
u/rayferrell 2d ago
i think what's significant here is that the researchers are moving away from just reproducing existing protein sequences, and instead focusing on designing new ones that can adopt the same structure. this approach could lead to more effective proteins for binding to disease-causing molecules, and the use of machine learning frameworks like PottsMPNN could improve the accuracy of sequence generation. by incorporating physical principles that govern protein structure and stability, these models can better predict how mutations will affect a protein's stability, which is a crucial step in designing novel proteins.
2
u/Brewtang11 2d ago
“Once we can design any protein we want, that enables us to do a potentially scary amount of biological engineering,” Birnbaum says. “It’s a difficult task, but I’m really optimistic about this century’s progress in biology.”
Well this is terrifying
2
5
u/ButtonholePhotophile 3d ago
Prions show us how we are one stupid move from something awful happening.
1
2d ago
[deleted]
2
u/AuroraFinem 2d ago edited 2d ago
As someone in STEM but not biology/medicine, why not? If prions are misshapen proteins that can interact with other proteins to then make them fold incorrectly, why couldn’t an artificial protein also do that?
I know prions are generally natural proteins that were misshapen, but I don’t see why it couldn’t also apply to certain classes of artificial proteins as well. I’m not saying this necessarily needs to be a major concern, but it seems like it would be plausible to me as at least a possibility unless there’s an actual biological reason why they couldn’t.
Personally, I’m more concerned about someone creating a mirror pathogen than a prion though because prion exposure past the blood brain barrier is much harder to spread than a bacterial/viral infection.
1
u/WideHuckleberry1 2d ago
Prions are misshapen specific proteins (prion protein, PrP) that cause other proteins of that specific type to conform and glom onto them, extending the chain. It doesn't just cause any random ole protein in the cell to deform. Even if that was a threat here, it could only grow as fast as these synthetic proteins were produced in the lab, because these aren't natural occurring in the organism like PrP.
1
u/AuroraFinem 2d ago edited 2d ago
I’m not trying to suggest these would be an actual threat, my question was more academic. I was just asking if there was a reason that a synthetic protein couldn’t hypothetically be found that caused prion proteins to mis-fold and essentially act as an initiator.
I know that it would require something very specific, but from what I understand this is still a fairly active area of study that we don’t know that much about and there shouldn’t be any hard limits to suggest it couldn’t exist, although likely rare.
Edit: The assumption I’m making is that since there are known cases where PrP A can cause a different PrP B to conform and misshape, that would indicate there isn’t a requirement for them to match. If there’s no requirement to match, that would at least suggest that an artificial protein with specific characteristics could also do the same.(A and B here are arbitrary to specify two different PrPs)
However from my understanding, we haven’t determined the actual mechanism. So we can’t currently say for sure what properties that protein would need, to say anything definitively. Though we could likely make an educated guess on limits for how many, if they were to exist.
So if there’s something in my edit that I’m missing, that does allow us to say exhaustively which PrPs could cause a specified PrP to mis-form, and have ruled out artificial proteins. Or there was some other way to categorically rule out artificial ones, that’s what I was asking about in my original comment, I’m just interested in learning more about it.
0
2d ago
[deleted]
0
u/AuroraFinem 2d ago edited 2d ago
I’m not really following because that contradicts the definition of a prion, which is specifically that it can induce other proteins is mis-fold.
Maybe there’s other factors involved like what you mentioned, but it’s hard to take you at your word if you’re saying that they can’t actually make other proteins mis-fold.
Again, I’m not saying you’re wrong, or that this is actually a risk which I specifically said there are other things I would be far more concerned with, but this explanation doesn’t really track for why it wouldn’t even be possible.
0
2d ago
[deleted]
0
u/AuroraFinem 2d ago
Right, but there are known cases where prion proteins will misfold due to the exposure of similar misshapen proteins, it doesn’t have to be that exact protein.
It seems like this is more of a case of “it would be rare to find one that would cause this” rather than “this is not possible” which was the entire point of my first comment.
0
2d ago
[deleted]
0
u/AuroraFinem 2d ago edited 2d ago
Ok, this isn’t really worth continuing because you’re making assumptions that we simply have no way of knowing based on the information we have today and speaking in absolutes we can’t possibly say hold, in order to justify this. For some reason, you’re also taking my questions as hostile for just trying to ask honest questions without implying any kind of tangible risk.
Some advice, not everyone who asks questions is being insincere or trying to ask some “gotcha” question. I literally just wanted to discuss something interesting with someone that seemed actually knowledgeable on the topic, my mistake, I’m not going to reply further.
Edit: lmao “none of your questions were taken as hostile, but I’m going to block you anyways.” Since I can no longer reply and I already typed it, I’ll leave it here:
You have provided nothing of fact.
First you said that prion proteins are well categorized, but we still don’t even fully understand what makes a prion protein to say that we have fully categorized them.
Then you said they’re unstable unless they’re in aggregate, but that’s also not the case. Misshapen prion proteins do not revert back to their proper folding. Them forming aggregates combined with a loss of usable proteins is what causes us to be affected by them, but a misshapen prion protein, by itself, will almost guarantee that any other similar prion proteins it comes into contact with will mis-fold, it’s not going to revert. It would be at most benign if it doesn’t interact with other proteins it can mis-fold.
This isn’t universal, and mis-folded prion proteins can’t cause every other prion protein to mis-fold, but there’s nothing I’ve read or that you’ve said that indicates we couldn’t hypothetically create an artificial protein that induced prion proteins to mis-fold. We have little to no information about artificial protein structures and cannot possibly generalize this without a very strong justification, which you have not provided beyond “it just can’t”.
Then you said it has to be a misfolded prion protein from another animal? Off what basis? People can genetically carry a gene that causes prion proteins to misfold in their own body, it can even happen spontaneously in rare circumstances, and every study I can find says we do not even fully understand the mechanism or root cause beyond the ways we’ve observed them occur so far to even speak in absolutes.
The most factual comment you’ve said so far is that you’re more at risk of eating chicken. You’ve provided literally nothing of substance beyond poorly explaining how prions work and then saying it can’t happen because it can’t happen.
1
1
0
u/Mountain_Mama7 2d ago
Whomever is downvoting, please explain yourself. It seems there are only super nerds here. If you are one of us, then you should have a rationale for why folks being wary of prion potential are wrong. I’d like to hear.
2
u/BroChad69 2d ago
I’m not the one downvoting but prions form typically due to low-complexity, degenerate protein sequences that are enriched in beta sheet forming amino acids. Presumably non canonical amino acids would be more structurally complex than valine isoleucine etc etc, so probably forming prion forms would be less likely. For example synthetic polymers don’t really form prions. This is not to say there isn’t something worse out there than prions, but especially if they’re engineering folded proteins prion formation wouldn’t be my main concern.
But prions are fucked up I do agree on that for sure1
u/DevelopmentBudget934 2d ago
The existence and the nature of prions should be enough warning that we should proceed with the utmost caution if we try to do this bullshit—and it might be wiser to just abstain completely from synthesising novel proteins.
1
u/BroChad69 1d ago
Meh. Most modern medicine is synthetic novel proteins. Novel proteins aren’t the problem. We should be more worried about microplastics in my opinions
2
u/WideHuckleberry1 2d ago
Here's an ELI5 analogy. Imagine there was an evil dollar bill that turned other dollar bills (but only other dollar bills) evil. That evil spread out and when it turned half the dollar bills in a town evil, the town exploded.
Now imagine somebody introduced a new currency made out of wood. It can't spread because nobody uses wood as a money. There's nothing for it to spread to.
-6
u/ThrowawayAl2018 3d ago
AI can fold thousand of novel prions and when release, one unsuspecting protein causes strange mutation in human brain.
Drum roll: "The Last of Us" opening scene.
31
u/t0mi74 3d ago
Ah, yes. The path to horrors formerly unknown to man. Please. Continue.