[HN Gopher] Some Proteins Change Their Folds to Perform Differen...
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Some Proteins Change Their Folds to Perform Different Jobs
Author : pseudolus
Score : 86 points
Date : 2021-02-04 11:53 UTC (11 hours ago)
(HTM) web link (www.quantamagazine.org)
(TXT) w3m dump (www.quantamagazine.org)
| chromanoid wrote:
| I don't like the headline. As if the protein decides to do so.
| Maybe this sounds a little bit less "active" but probably also
| less sensational: "Some Proteins Perform Different Jobs By
| Changing Their Folds"
| natechols wrote:
| One of my pet peeves is science journalism abusing the active
| voice, often in ways that almost anthropomorphize the process.
| The absolute worst are phrases like "Nature designed this
| protein to...", which I have seen otherwise reasonable,
| rational writers toss about carelessly. (It's like the inverse
| of the passive voice used to describe police shootings: "the
| suspect was hit by gunfire", etc.)
| 0_____0 wrote:
| A reasonable reader will implicitly understand that the
| proteins have not, in fact, acquired sentience.
| blix wrote:
| This is what I tell myself every time I read an HN comment
| written by a collection of proteins.
| nate_meurer wrote:
| I don't normally meta-comment on other comments, but this
| one is superb. It took me a moment to soak it in.
| natechols wrote:
| True! Problem is, there are a lot of unreasonable readers
| too, many of them having strong opinions about natural
| versus directed processes.
| passivate wrote:
| Well, you can't reason with unreasonable people :) That's
| the actual problem. Also, I strongly disagree with your
| view that a lot of them are reading scientific articles.
| The root problem is lack of science education/curiosity
| which needs to be addressed specifically, rather than
| forcing the rest of the world to adopt certain phrasing.
|
| Personally I like the romanticism/poetic style, it makes
| articles seem less bland, which makes me want to read
| them even more.
| uoaei wrote:
| Based on my experience with otherwise reasonable readers
| who are relatively naive when it comes to biology, this is
| not the case.
| jostmey wrote:
| Natural selection may not select for simplicity. It may not try
| to reduce dependencies. A gene can depend on thousands of other
| genes. And a gene can carry out multiple functions
| macksd wrote:
| Natural selection doesn't "select" for anything except the
| survival and continuation of species. Everything else that it
| _tends_ to favor is merely a correlation with that - so you
| have to expect a certain level of variation and exception.
| thaumasiotes wrote:
| > It may not try to reduce dependencies.
|
| This one's pretty straightforward; natural selection has two
| very common approaches to dependencies:
|
| 1. If the presence of something is not a reliable feature of
| the environment, dependence on that something will be
| ruthlessly weeded out.
|
| 2. If the presence of something is a reliable feature of the
| environment, dependence on that something will be created and
| grow to permeate most existing systems.
|
| The first effect has a lot of popular awareness; the second
| doesn't. They're both important.
| cmpb wrote:
| Counterargument to 2: the air is largely nitrogen, but humans
| do not utilize it during respiration. Thus, this reliable
| feature of the environment has not been selected as a
| dependency.
|
| I'm not necessarily arguing it's untrue, just not quite the
| hard-and-fast rule that 1 is.
| thaumasiotes wrote:
| > I'm not necessarily arguing it's untrue, just not quite
| the hard-and-fast rule that 1 is.
|
| This is pretty subjective. If you grow up with sufficient
| dietary iodine, that's worth 10-15 IQ points (a gigantic
| amount) compared to the counterfactual. Iodine
| supplementation is highly effective in populations that
| have presumably been going without for, at the very least,
| many hundreds of years. This is the reason we iodize salt.
|
| With that in mind, how much of a hard-and-fast rule is #1?
|
| The other side of this argument is that dependencies can be
| surprisingly subtle. This is pure speculation, but the
| thing that leaps out at me about atmospheric nitrogen is
| that oxygen is extremely corrosive. If the atmosphere were
| more oxygen and less nitrogen, lungs of today might
| experience a lot more wear and tear than they are currently
| designed for. (Or not! I really have no idea. But I think
| the hypothetical has some thought-experiment value anyway.)
| throwaway2245 wrote:
| Humans are systemically dependent on nitrogen in the air,
| in that it is required for nitrogen fixation.
| fabian2k wrote:
| How should we use nitrogen gas in the air? Oxygen is useful
| to us for energy production. Nitrogen we get from easier
| sources in different forms.
| jostmey wrote:
| > 1. If the presence of something is not a reliable feature
| of the environment, dependence on that something will be
| ruthlessly weeded out.
|
| Something is only weeded out if it is sufficiently
| _disadvantageous_. There are lots of examples in biology
| where mutations are neutral and allowed to accumulate. There
| is also a lot of junk DNA, and even though we 've found that
| some junk DNA was misclassified, there still is a lot of junk
| DNA in each genome
| thaumasiotes wrote:
| Dependence on something that isn't there is disadvantageous
| by the definition of "dependence". I don't see the point
| you're trying to make.
| sooheon wrote:
| Interesting. Any examples of the 2nd?
| jcims wrote:
| Honeybees, sunlight, water, oxygen, etc.
|
| Edit: Also -
| https://en.wikipedia.org/wiki/Radiotrophic_fungus
| matheusmoreira wrote:
| Another awesome example:
|
| https://en.wikipedia.org/wiki/Nylon-eating_bacteria
| londons_explore wrote:
| In mammals, the dependance on a certain body temperature.
|
| The fact that it is regulated to a margin of 0.3% shows
| quite how important it is. Increase or decrease the body
| temperature by 5% (on an absolute scale, so Kelvin), and
| you will be a dead human...
| JPLeRouzic wrote:
| A question from a layman: Could changing body's
| temperature by a few percent, for a small amount of time,
| be used to heal from some diseases, like cancer or
| diabetes?
| thaumasiotes wrote:
| Some diseases, yes; people do this all the time and it is
| called "running a fever". Fevers are not induced by the
| disease; they are a strategy you use to kill the disease.
|
| Cancer or diabetes, no. Diabetes is not even a "disease"
| in the sense of an organism that can be alive or dead.
| JPLeRouzic wrote:
| Thanks for the answer!
| thaumasiotes wrote:
| > The fact that it is regulated to a margin of 0.3% shows
| quite how important it is.
|
| This is an excellent point. It can be applied to a huge
| number of biological phenomena, but it almost never is.
|
| An example where this idea actually has made it into the
| mainstream is body weight. I read an article that pointed
| out that, yes, we're fatter than we used to be, but
| regulating body weight by measuring energy intake and
| expenditure is doomed to fail. Articles making this claim
| are a very rich genre, but I found the particular
| argument fascinating:
|
| People routinely maintain the same body weight, within
| say 5 pounds, for years at a time. This is a level of
| accuracy that we do not have the technology to achieve by
| using measurements of energy inflow and outflow -- we
| can't measure dietary energy that precisely! (And modern
| technology is, by most standards, _very precise_.)
|
| Thus, there is a very strong suggestion, based on this
| incredible stability, that your body is regulating itself
| to a certain weight. If you adjust energy intake, or
| outflow, other things will adjust accordingly; those are
| unlikely to be primary determinants of the system's
| behavior.
| adrian_b wrote:
| Yes indeed, there are examples of dependencies that have been
| removed by evolution.
|
| For example cobalt and nickel were both essential for the
| first living beings. However, on the continents they are much
| less accessible than in the oceans.
|
| Because of that, most terrestrial plants have lost the
| dependency on cobalt (which is why they cannot provide
| vitamin B12 to those who eat them) and most have also lost
| the dependency on nickel (except that for many terrestrial
| plants nickel, while no longer strictly required, can still
| be useful by enabling them to use urea as a source of
| nitrogen, when other sources of nitrogen are scarce).
| hamilyon2 wrote:
| Inevitable becomes necessity.
| throwaway2245 wrote:
| In my opinion, the second is just not true.
|
| If a reliable feature is evolutionary advantageous, then new
| systems will come about to take advantage of that (and may
| out-compete old systems, indeed, to the point of extinction),
| I agree.
|
| But, if a reliable feature isn't evolutionary advantageous,
| it can be ignored or even removed.
|
| Negative features may need to be managed, rather than taken
| advantage of. Examples: ionizing radiation, landfill.
| [deleted]
| jugg1es wrote:
| I feel like I remember hearing this as an undergrad neurobiology
| major 15 years ago. Is this even new?
| dnautics wrote:
| it's just a slightly more extreme form of the glove-and-hand
| principle (versus lock and key). Of course even this turns out
| to be a spectrum. there are enzymes/protein that are more lock-
| and-key, and proteins that interact very heavily. One extreme
| is insulin receptor (which totally mangles insulin out of shape
| on binding). IIRC, another interesting one is antibody
| evolution, as B cells mature they go from producing antibodies
| that are gloves-in-hand to antibodies that are lock-and-key, as
| measurable using IR spectroscopy:
| https://www.pnas.org/content/103/37/13722.short
| Rochus wrote:
| Yet another challenge for AlphaFold.
| hprotagonist wrote:
| After long study, my iron-clad law of biology is this: every
| _other_ iron-clad law of biology ends with the phrase "well,
| except when ..."
| tejtm wrote:
| This. Decades ago I once innocently noted
| Biology is a system of exceptions!
|
| still hear the echos.
| infogulch wrote:
| This seems to apply to your law as well.
| hprotagonist wrote:
| isn't it great?
| grishka wrote:
| As a software developer, I find biology to be fascinating but
| at the same time extremely complex and counterintuitive.
| Everything seems to be influencing everything else in subtle
| ways. You can never separate an organism into distinct modules
| that do distinct jobs and expose distinct interfaces, like you
| could a program or a hardware device when reverse engineering.
| The fact that physics and chemistry are being exploited in most
| unexpected ways doesn't help either.
|
| But then the thing to remember is that biology is alien
| technology in the sense that it wasn't created by humans and is
| still ahead of our current technological progress. It's the
| only alien technology we've been able to get our hands onto.
| WJW wrote:
| Mother Nature only cares about energy efficiency and
| evolutionary fitness. If that means every variable has to be
| global, so be it. She is not coding with understandability in
| mind.
| nobodyknowsyoda wrote:
| I'm probably preaching to the choir, but yup that inherent
| uncertainty seems to distinguish biology from the other
| sciences. There is a huge stochasticity & serendipity in
| everything because there is no intentionality in the design of
| any biological component; any convergence toward a chemically
| or physically optimized component or behavior is driven by
| evolution by natural selection but remains imperfect. Warts,
| quirks, and all
|
| It also explains how the folks on HN positing "Covid is just
| the flu" and "long Covid isn't real" have been so confident yet
| so gravely mistaken. They are used to other sciences where
| there is much less room for uncertainty
| hprotagonist wrote:
| Yep. For better or worse i've been up to my eyeballs in "hey,
| you know, biological systems are actually insane!" since high
| school, and now through a few advanced degrees :)
|
| I've been working in tech more than normal for a few years
| now, and the endemic nature of "the andy grove fallacy" among
| my coworkers has ceased to startle me, but it's just kind of
| bothersome every time.
|
| https://blogs.sciencemag.org/pipeline/archives/2007/11/06/an.
| ..
| nitrogen wrote:
| Despite the common trope that software/hardware engineers
| think they understand everything, automation can make
| exponential development possible in bio. I know someone who
| works at a biotech company, and the stories I hear lead me
| to believe that traditional thinking in e.g. medicine and
| insurance, and from colleagues, really is a bottleneck.
| Maybe exponential growth will never apply to the number of
| diseases cured, but it can and should apply to the hardware
| and software that facilitates the next iteration of
| biological discovery.
| hprotagonist wrote:
| It's not that software/hardware engineers think they
| understand everything, it's that the absolutely common
| idea "my way of thinking about understanding things is
| appropriate in this other domain" breaks down very fast.
|
| I'm not speaking about running hospitals or dancing with
| insurance companies. I'm speaking about much earlier in
| the pipeline: fundamental, blue-sky biological research
| is fundamentally different from software. The reason is
| that we are not studying designed systems; the effect is
| that there is so much that we don't know that we don't
| know that things that sound easy are in fact basically
| impossible because the prior knowledge is simply not
| established. (Until they aren't. When does that change?
| First slowly, then all at once.)
|
| As a biomedical engineer, i'm on board with hardware and
| software improvements: it's kind of my job. The trick is
| knowing what you're doing, what you aren't, and what you
| can expect, and to balance confidence in the value of
| what you _can_ tightly constrain and design versus
| humility in accepting that the natural world simply
| doesn't care.
| natechols wrote:
| I think what bugs me the most is the common assumption
| that we just need better modeling tools to make a lot of
| the messy lab work go away. Everyone who raises this idea
| seems to think it's original and revolutionary and a no-
| brainer, but there's at least 40 years of bitter
| experience in biotech and pharma development saying
| otherwise. Even genuinely impressive feats like AlphaFold
| get inflated wildly in importance (and used to
| retroactively bash experimentalists for all the time they
| wasted by not listening to software people). Actually
| speeding up the entire process of biomedical research
| requires improvements across the board in many different
| fields, and it's not something that is magically going to
| be solved by computer science wizardry alone.
| hprotagonist wrote:
| I primarily do modeling, and I am first in line to tell
| anyone who is willing to listen that the very first thing
| you should do to learn to be a good modeler is spend a
| year at the bench first in the problem area you want to
| model.
|
| Wet lab is so informationally dense in terms of personal
| knowledge that it's not even funny.
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