A protein folding mystery solved: Study explains core packing fractions
phys.org
phys.org
Why is the packing fraction 55% maximum (in globular proteins)? "The answer seems to be that the packing fraction stops increasing when the protein cores jam or rigidify." Ok, so ...
> "That is, the individual amino acids that make up the protein core couldn't compress any further when the protein folded"
So they can't pack any further because they 'jam'? Ohhh, from the abstract of the paper:
> "... However, important developments in the physics of jamming in particulate systems can shed light on the packing of protein cores. ... Then, we develop an all-atom model for proteins and find that, above ∼0.55, protein cores undergo a jamming-like transition"
Possibly this is related to the need for protein cores to remain relatively 'liquid', as enzymes (for example) need to be somewhat flexible when binding/releasing substrates. A fully 'jammed'/packed core would lead to an inflexible structure with lower ability to ... er... move, bind stuff (I'm handwaving here :) )
"The authors acknowledge support from NIH Training Grant No. T32GM145452 (A.T.G., C.S.O., and Z.L.), NIH Training Grant No. T15LM007056-37 (J.A.L.), and the High Performance Computing facilities operated by Yale's Center for Research Computing."
All of these things (the NIH and Yale's Center for Research Computing) relied so heavily on government funding that they are no longer getting, especially if they don't sing ideologically pure songs for dear Leader.
It very much will be the dark ages if the only money available for research is at the mercy of industry. It probably won't be dark ages for the whole world -- just the countries that squander their research advantage. Brain drain from the US is already starting. Hopefully there will be a clear cease and desist message sent to this regime when the people vote again Nov 2026.
I really don't get this level of hyperbole. There's so much hand-wringing about funding getting cut, but it turns out it's like a 15% reduction[0]. That's not an insignificant amount, but it's not the end of the world. Taken naively, that's 15% less research that gets done. One can hope that, being a pillar of academia, the intelligent folks over at Yale can figure out how to spend 15% less on research, so the same amount of research gets done with fewer dollars. Or, better yet, they can put more effort into finding and cutting the rising levels of fraud amongst academic researchers[1].
I think 15% might be too drastic, but at the end of the day, things can't always progress up and to the right, all day every day. If you don't want waste, you sometimes have to cut things, or at the very least apply pressure to them. This mindset of "any cut is bad!" prevents necessary cuts, especially when coupled with this "everyone gets a voice" mindset, simply because you can always find someone to speak up in protection of anything--even fraud! I'd say you'd be surprised by how vigorously people protest their own innocence when they're clearly participating in bad behavior, but like... _gestures at everything_
Don't get me wrong, I think this administration is going about this in mostly the wrong ways, but the problem is, they're doing something those in the affected academic organizations refused to do, namely: applying sufficient adversity to the system to keep it strong.[2] The fact that fraud among scientific research is increasing over time is ample evidence that they're not doing enough to self-police. I don't know how rigorously studied the phenomenon is, but I've certainly seen an increase in popular science coverage of various frauds and scandals in all kinds of scientific fields over the years. Should we really continue paying and promoting the people who are perpetrating this fraud? (As an aside, I wonder how much money is given back to the government when fraud like this is exposed before the grant is fully filled? Or does it usually escape detection until after the grant has been paid out? Anyone know this?)
When you depend on someone else funding your studies, but don't do sufficient legwork to keep things operating smoothly, why is it a seemingly the end of the world for the organization providing the funding to decide to cut it? This is essentially the ruling demographic says: "we think you're wasting our money, so we're going to give you less of it until we see you do better". I think this is a personally reasonable ask! I think the definition of "do better" is troubling in some cases, but this sort of thing should be happening all the time. I don't understand why you and seemingly so many others seem to think that the government shouldn't ever be cutting funding to research programs, especially when the level of waste just keeps going up? You and others constantly hyperbolize a (admittedly large) cut into "oh no it's the end of the world". But it really isn't, and it's not even really an insurmountable challenge. Run a few plagiarism/LLM checks, fire/expel the worst offenders, and you've already saved a significant fraction of the newfound deficit! Yeah, you might destroy some "promising" careers, but look: attempting to deceive the entire world for personal gain (even if just to maintain a basic standard of living!) probably should come with a pretty stiff penalty. The kind of person who would falsify data for personal gain is only promising to do more of the same for their whole career. They're exactly the kind of people that academia should be vigorously expelling.
To look at it from another angle: Academic research needs to be built on a foundation of trust. There will also always be adversaries in the system, and how hard they have to work to stay hidden is dependent on how much oversight there is. If the oversight is lax, adversaries can thrive, which ultimately erodes trust both within the system and without. If academia (as a nebulous whole) is not doing enough internal oversight to keep adversaries in check, then it falls to those outside academia to try affect this oversight. Given the current capitalistic nature of our society, this tends to come in the form of withholding or cutting funding. The more the trust erodes, the stronger the external response, which is what I think we're seeing today. But while a 15% cut might be "too far" or "too much" or "too inaccurate in allocation", consider that part of the reason these cuts are happening is because those "outside the system" have lost trust in the academic system in this country. In response, they did what they could: elected adversaries of the system as it exists today.
And why have the people who support these cuts lost trust in the academic system? Abstractly, I think this boils down to the contrast between this apparent lack of internal oversight and the nature of academia itself: the pursuit of knowledge. Academia literally exists to discover new truths and present them to the rest of the world. It asks the rest of the world to subsidize this learning in various ways, with the promise that the newfound knowledge will vastly repay the subsidy. But when the knowledge the academic system is putting out is increasingly found to actually be bullshit, it repeatedly breaks this promise.
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Anyway, that's a lot of words to say I think your opinion is wildly hyperbolic and immature. I'm getting tired of folks defending an obviously imperfect system as if every small attack on it is "the end of democracy!" It's not helpful, and it just reinforces the image that folks who hold the same beliefs as yourself are also likely to be equally hyperbolic and immature. It's not a good look.
[0] https://yaledailynews.com/blog/2025/02/10/nih-slashes-indire...
[1] https://retractionwatch.com/2024/09/24/1-in-7-scientific-pap... unsure the quality of this source, but fraud in research is definitely a thing I've been hearing more and more about, especially with generative AI getting let loose on it by folks with... looser morals
It's worth keeping in mind that the loudest complainers are often the ones with the most to lose; and those with the most to lose are often the ones taking advantage of waste and bloat.
To take a trivial example, look what happens any time there's a ban wave in a popular online game: people come out of the woodwork complaining about how they were unfairly banned, were a false positive, etc... and then you ultimately find out that yes, they were indeed cheating and were caught.
Complaining loudly when caught cheating or threatened with enforcement is basically human nature. The fact that people complain loudly when the gravy train runs off the rails isn't much different, and the complaints should honestly be taken with a grain of salt.
Suffice to say, it's worth considering whether the cost of a decision can be interpreted solely as how much money there is vs the wider ecosystem level consequences of said decision.
I take a lot of these arguments with a grain of salt. As a society, we've gotten way too used to substituting plausible hypotheticals for concrete data.
> Run a few plagiarism/LLM checks, fire/expel the worst offenders, and you've already saved a significant fraction of the newfound deficit!
This is absurdly reductive, and doesn't connect with the genuine issues at play incentivising good research and detecting fraud.
I don't think your sweeping statements are true though, either? Every social endeavor, when allowed to grow without adequate pressure, becomes bloated, slow, and full of waste. This is almost universally true, and the exceptions tend to be things where there is heavy pressure to be lean. This pressure is more effective when it comes from within, but external pressure works, too.
If you want a process to remain efficient over time, it either needs to start that way and not change, or be aggressively pruned from time to time.
Academia should be pruning the waste and fraud itself, but is clearly not doing so aggressively enough.
I agree that the cuts, if naively applied, will cut both good research and bad. On the other hand, I think if academic research institutions are doing things naively, they're doing it wrong.
> This is absurdly reductive, and doesn't connect with the genuine issues at play incentivising good research and detecting fraud.
Of course it is! But the fact that academia seems to be utterly failing at performing even the most basic checks against fraud routinely. Of course a reductive approach is insufficient, but it would be better than the current status quo, which is to implicitly support the fraud by refusing to even look for it in the first place.
And it's honestly not any more reductive or incorrect than this:
> Harsh cuts in funding always penalise blue sky research, controversial work and anything that isn't guaranteed to bring press to the funding institution.
Well, NIH training grants aren't going anywhere, so far as I know, and the high-performance computing facilities may or may not be affected by a cut in indirects. If they are affected, one reasonably has to ask: what line items made it past the cut? It's a more productive framing of the question.
Either way, you can't just leap to the conclusion that everything you like will be gone.
> especially if they don't sing ideologically pure songs for dear Leader.
I think it's possible that you're exaggerating.
One grant started in 1987 and has extensions running into 2027 for dozens of different sub-projects. Total award so far has been $13.1m. The other grant is for up to $800k over 5 years for 5 student positions ostensibly worth $32k per year. The YCRC seems to be funded directly by Yale.
https://www.highergov.com/grant/T32GM145452/
https://www.highergov.com/grant/T15LM007056/
> sing ideologically pure songs for dear Leader.
Hot take; however, perhaps the energy put into this ideological signalling could be better spent on working to solve what is a relatively small problem.
This is not true. There are some proteins that are intrinsically disordered, not folding into any preferred way, but they still perform biological functions.
https://en.wikipedia.org/wiki/Intrinsically_disordered_prote...
It is hard to think of an example without sounding like I am exaggerating. Imagine if you shared on a thread that Rust has a great ecosystem but it is a little bit too overhyped and someone so cleverly asked for you to cite sources.
Do you really rely on academic studies to form any impression of anything? Is your chain of thought full of citations?
I have this screw I want to undo but Schonenberg et. al. has demonstrated that a Philips screw should be used for this situation. Unable to find any citations on the feasibility of a blunt knife in this situation. Further research needed.
I was then asked about sources for what amounts to an easy homework problem.