[HN Gopher] A protein folding mystery solved: Study explains cor...
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A protein folding mystery solved: Study explains core packing
fractions
Author : PaulHoule
Score : 83 points
Date : 2025-04-14 13:36 UTC (2 days ago)
(HTM) web link (phys.org)
(TXT) w3m dump (phys.org)
| ChuckMcM wrote:
| This is the kind of cool stuff I'm going to miss during the
| coming dark ages. When ever I read this in a paper:
|
| "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.
| user32489318 wrote:
| Researchers will seek other opportunities, there are other non-
| US grants and support structures. While studying in EU, I knew
| quite a few PhDs who secured substantial financial aid from the
| industry directly, on their own. Yes, it will get trickier, and
| will steer the research in a certain direction. But I won't
| call it the dark ages.
| daveguy wrote:
| Ah yes. Industry funding. We all know how independent and
| dedicated to the scientific pursuit of truth industry funded
| research is.
|
| 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.
| try_the_bass wrote:
| > This is the kind of cool stuff I'm going to miss during the
| coming dark ages.
|
| 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.
|
| ---
|
| 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
|
| [2] https://www.apa.org/topics/resilience
| fabian2k wrote:
| It is a lot more than 15% cuts. The latest numbers I saw
| about grant approvals were something like only half of the
| number of approved grants compared to the same timeframe last
| year. On top of that you have the cap of indirect costs at
| 15%, which is alone more than what you describe. And on top
| of that are the other ways they are interfering with
| research, e.g. by the draconic spending limits on credit
| cards and other arbitrary ways they are blocking money from
| getting spent.
| hengheng wrote:
| In any other industry, a 15% cut would be Bad News, and
| people would be talking about ripple effects, they would call
| it a "shock" and talk about the long-term consequences.
| agoose77 wrote:
| I want to be careful about what I write given the context of
| what's going on, and the personal ramifications that can
| have.
|
| 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.
| dbspin wrote:
| The fraud issues you mention are real and pressing... They're
| also completely disconnected from blanket cuts to NIH
| funding. There seems to be some kind of grasping for a
| positive in heavy cuts to essential research here. Put
| another way, there is zero selective pressure for 'less
| fraudulent' research to be cut. If anything, this applies
| selective pressure on publish or perish, false positive,
| press release style research. Harsh cuts in funding always
| penalise blue sky research, controversial work and anything
| that isn't guaranteed to bring press to the funding
| institution.
|
| > 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.
| timr wrote:
| > "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."
|
| 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.
| jibal wrote:
| Lots of things are possible while clearly not true, and
| that's one of them.
| timr wrote:
| Well, pretty much everything in the comment I replied to is
| untrue, so technically the entire comment falls in that
| category.
| timewizard wrote:
| > relied so heavily
|
| 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.
| esbranson wrote:
| Well we're certainly not going to see any European institutions
| step up, despite their propaganda to the contrary.
| banq wrote:
| The research direction has gone off track--it's overly fixated on
| proteins "chasing fireworks" (metaphorically trivial pursuits),
| while mitochondrial and other molecular pathways represent a far
| more substantial and impactful frontier. The academic world is
| mired in stagnation and decay, demanding external pressure to
| break its complacency.
| refactor_master wrote:
| No sources cited?
| therein wrote:
| It comes across borderline comical when a man gets asked for
| his sources while he is clearly stating his formed opinion
| based on his impressions.
|
| 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.
| thaumasiotes wrote:
| There was a thread on HN semi-recently where I observed
| that if you think about classifying complexities ("big-O of
| n squared") by polynomial degree (so we think of O(n^2) as
| "2"), the logarithm function gives you a literally
| infinitesimal value.
|
| I was then asked about sources for what amounts to an easy
| homework problem.
| gilleain wrote:
| The 'explanation' in the article is a little thin:
|
| 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
| :) )
| timdellinger wrote:
| for perspective, monodisperse spheres max out at 74% (hexagonal
| close packing)
| pfdietz wrote:
| "In living organisms, every protein--a type of biological polymer
| consisting of hundreds of amino acids--carries out specific
| functions, such as catalysis, molecule transport, or DNA repair.
| To perform these functions, they must fold up into specific
| shapes."
|
| 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...
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