[HN Gopher] Proteins, Proteins Everywhere
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Proteins, Proteins Everywhere
Author : nabla9
Score : 71 points
Date : 2021-12-25 10:33 UTC (12 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| ralusek wrote:
| There needs to be further collaboration between computer
| scientists and these emerging biological platforms. Between the
| ability to synthesize code (RNA) and data (protein), I don't
| think it's been fully realized by most that they've truly entered
| the world of computing.
| itg wrote:
| Isn't this what the entire field of bioinformatics supposed to
| be about? I know a few people who left it because it doesn't
| pay as well (in the US) as your average software engineering
| job.
| gilleain wrote:
| I have seen a distinction made between "bioinformatics" -
| analysing biological data with software - and "computational
| biology" - using biological systems to do computing.
|
| What OP seems to be talking about is systems modelling, where
| you model the network of genes and proteins (genomics and
| proteomics) using tools partly derived from modelling of
| computer networks.
| epgui wrote:
| That's not how I would explain bioinformatics and
| computational biology... What people often mean when they
| say bioinformatics is actually computational biology: using
| computer software, algorithms and other such tools to
| analyze biological data. Bioinformatics is the development
| of new tools, new algorithms and new methods to do
| computational biology.
|
| In other words, a bioinformatician is to a computer
| scientist what a computational biologist is to a data
| scientist.
|
| Using biological systems to do computing is more in the
| realm of "biological computers".
| gilleain wrote:
| Yes and no. Biological systems are similar to mechanical
| computers in that they are information processing systems.
|
| However, they are also self-assembling, self-repairing, wet,
| massively parallel, etc. Artificial biological systems are in a
| sense programmable, but with the difficulties of a physical
| system that can be error-prone and extremely complex.
| netizen-936824 wrote:
| Don't worry, we are. But it does seem slow compared to other
| tech industries
| COGlory wrote:
| You may be interested in this:
|
| https://pubmed.ncbi.nlm.nih.gov/30237357/
|
| Programmable protein circuits in living cells
| COGlory wrote:
| >This "protein-folding problem," as it came to be known, baffled
| scientists until this year, when the papers we've deemed the 2021
| Breakthrough of the Year were published.
|
| This is a straight lie and the author should be embarrassed.
| There's not one scientist alive that can explain how proteins
| fold from their amino acid sequence. There's not one algorithm in
| existence that can predict it de novo.
|
| I'm so tired of seeing this lie repeated over and over. AlphaFold
| did not gain us any new information on how proteins fold. It just
| got really good at modelling them from existing data where
| existing data is available. Which is great. But still ultimately
| limited by the same categorical limitations of homology modeling.
| It simply has not solved protein folding.
|
| Yes it's amazing.
|
| Yes it's worthy of lots of praise.
|
| No, it did not solve protein folding, ESPECIALLY in the way that
| is described here.
| epgui wrote:
| > There's not one scientist alive that can explain how proteins
| fold from their amino acid sequence.
|
| As a biochemist, what I understood from this editorial was
| totally reasonable:
|
| - scientists understand that electrostatic forces guide protein
| folding, and steric factors limit the conformations a protein
| can take
|
| - scientists understand that the primary structure determines
| the secondary and tertiary structures of proteins
|
| - scientists know that protein folding is aided by chaperone
| proteins
|
| - scientists understand how thermodynamics and entropy affect
| protein folding
|
| Despite all of the above, scientists cannot solve protein
| folding de novo. New tools now allow us to make better, cheaper
| predictions which are testable.
|
| Sounds reasonable to me.
| COGlory wrote:
| As a structural biologist, I have to ask, how did you draw
| that from this?
|
| > seemed possible that the three-dimensional structure of a
| protein could be predicted based on the sequence of its amino
| acids.
|
| That simply is not what AlphaFold (or any homology modeling)
| is doing, and certainly not:
|
| >This is a breakthrough on two fronts. It solves a scientific
| problem that has been on the to-do list for 50 years. And
| just like Fermat's Last Theorem or gravitational waves,
| scientists kept at it until it was done.
| epgui wrote:
| > That simply is not what AlphaFold (or any homology
| modeling) is doing
|
| I don't know if we're getting hung up in semantic
| differences, but how would you describe homology modelling,
| or what AlphaFold is doing? Because for me, it takes as
| input an AA sequence and gives as output a 3D structure
| prediction.
| COGlory wrote:
| It's not a semantic difference. That's the problem. There
| is a difference between knowledge of protein folding
| (which is what the article is talking about), i.e.
| understanding proteins well enough to predict how they
| will fold, and modeling a folded structure (which is what
| AlphaFold is doing, based off of other pre-existing
| experimental structures).
|
| AlphaFold isn't simulating folding at all. It's modeling
| what the final structure should look like based off other
| data, not knowledge of how a protein folds. That's what
| is frustrating me so much with this topic. It's being
| sold as "we can predict how proteins will fold" as
| opposed to "we can model a folded protein based on its
| sequence". There's a huge difference in our understanding
| of protein folding, between those two points.
| epgui wrote:
| It does sound like a semantic difference. To me, and I
| believe to most in the field, the protein folding problem
| was always pretty much about figuring out the final 3D
| structure (the final state), and not necessarily about
| the _act of folding_ (ie.: the gerundive) itself.
|
| There is a lot of value in learning more about folding
| (in the gerundive sense), but the focus has always been
| on finding the folded structure, because as you very well
| know, structure is function.
| DisjointedHunt wrote:
| Reading this story gives me SO much hope for where we are as a
| society at the moment. It also gives me immense reason for pause
| to ask how many people out there with great ideas presently do
| not have access to the tools outlined in the story.
|
| We need, now more than ever, an "eli5" or "get up to speed in an
| hour" source for these very interesting fields where all the
| progress of the past century is easily visualized at a high
| level. I get the feeling much of academia shuts down such
| attempts to preserve their grip on knowledge and thus their
| authority.
| jryb wrote:
| > I get the feeling much of academia shuts down such attempts
| to preserve their grip on knowledge and thus their authority
|
| There might be fields like that, but in biology, it really just
| is that we've accumulated so much knowledge over the past 150
| years that I genuinely can't explain modern CRISPR research to
| a layperson until they've taken courses in molecular biology,
| microbiology, chemistry, genetics and biochemistry (or the
| equivalent amount of self-study).
|
| The field is genuinely vast and complex, and there's no way to
| hide that complexity behind an abstraction without being
| misleading.
| netizen-936824 wrote:
| This is a point echoed by professors I've met as well. The
| complexity of biological systems is quite hard to understate.
| There's such an immense amount of detail and almost none of
| it can be written off an unimportant.
| epgui wrote:
| > and almost none of it can be written off an unimportant.
|
| I just wanted to say that this is immensely under-
| appreciated, even by most people in the field. The more you
| learn, the more you realize that everything matters and
| every little bit of knowledge connects to a bunch of other
| knowledge.
|
| Most people in undergraduate classes ask "what part of the
| textbook is important" or "what part of this is on the
| exam", or even "what part of this will I need to know for
| my job", but they have the wrong attitude altogether.
| gumby wrote:
| > I get the feeling much of academia shuts down such attempts
| to preserve their grip on knowledge and thus their authority.
|
| There's no need to go all conspiracy theory on it. "People who
| like doing things like doing them", i.e. if you like doing
| protein chemistry you probably like talking about it with other
| people who do, but aren't really into, or don't even know how
| to talk to people who _aren't_ into it. The closest to that
| you're likely to get is writing grant applications, which are
| typically read by people who's are generally knowledgeable
| about your domain.
|
| The kind of translation you're talking about is itself
| generally the domain of specialists, such as science
| journalists.
|
| And as for "preserving their grip": typically institutions are
| the opposite, doing their best to get the message out, all to
| better their reputation and improve probability of grants and
| donations. That's what university press offices do.
| netizen-936824 wrote:
| Some fields are insanely hard to get caught up that simply and
| quickly. There's such an immense amount of detail in
| biochemistry that it can quickly become overwhelming to sort
| through information to find what's really pertinent. I'm not
| saying it's impossible, but it is definitely a huge challenge
| Ovah wrote:
| Tangent: I have years of academic studies. And yet it can be
| time consuming to truly understand where and how ideas came to
| be. I might have an equation but to understand how it was
| initially thought of or derived might require access to
| physical contemporary books. At least once I've had to resort
| to 18th century handwritten manuscripts. Wikipedia can be
| great. But I often wonder if historical scientific progress can
| be made even more accessible.
| alexpetralia wrote:
| This etiological approach is captured, for example, in the
| book "Inventing Temperature" by philosopher of science Hasok
| Chang. It chronicles the meandering, dialectical and
| controversial journey scientists pursue in order to discover
| what exactly temperature is - now elegantly captured in
| concise but sterile formulas. It demonstrates the _process_
| of science, as opposed to merely its output.
| 323 wrote:
| refurb wrote:
| Such a BS cop out. When I was doing my PhD, we were all
| training to pick apart the science. All challenges well come,
| as it forced our work to be airtight as possible. That's why
| the final process of a PhD is your thesis "defense".
|
| To somehow claim that we should just shut up and accept what
| the government says because "its based on science" is silly.
| Science changes, science is sometimes wrong.
|
| But we should also make clear that science results in policy
| and policy can be criticized without challenging science.
|
| "Yes, vaccines are effective, but no we shouldn't force people
| to take them" is a policy objection, not a scientific
| objection.
| embik wrote:
| I think it would make sense to provide sources with those
| quotes from March.
|
| I'm admittedly not from the US so I had different scientists
| talking about the pandemic, but around here 70% vaccination was
| never considered enough.
| fsagx wrote:
| _In the pandemic's early days, Dr. Fauci tended to cite the
| same 60 to 70 percent estimate that most experts did. About a
| month ago, he began saying "70, 75 percent" in television
| interviews. And last week, in an interview with CNBC News, he
| said "75, 80, 85 percent" and "75 to 80-plus percent."
|
| In a telephone interview the next day, Dr. Fauci acknowledged
| that he had slowly but deliberately been moving the goal
| posts. He is doing so, he said, partly based on new science,
| and partly on his gut feeling that the country is finally
| ready to hear what he really thinks._
|
| https://www.nytimes.com/2020/12/24/health/herd-immunity-
| covi...
|
| https://www.medpagetoday.com/opinion/vinay-prasad/90445
| hutzlibu wrote:
| "and partly on his gut feeling that the country is finally
| ready to hear what he really thinks"
|
| When you start doing stuff like that, you stop speaking as
| a scientist, but as a politician.
| DisjointedHunt wrote:
| Precisely. I'd like the scientific community to begin treating
| their declarations with the respectful humility science needs.
| Too often have i been reading headlines such as "The Universe
| is growing faster than it should" or "How science tells us the
| Pandemic will end once everyone is vaccinated". .
|
| . .or other such pop science cult rubbish. We do NOT know
| everything, we merely have "best fit" theories that are taught
| with the disclaimer that these work under specific conditions
| that we've observed and we have no way of gaming out all the
| trillions and trillions of possible outcomes in the real world.
| Trusting the common man with that level of transparency and
| then making humble "recommendations" seems a far better
| approach.
|
| Should we need to ram through a scientific conclusion, lets do
| so without making obviously uncertain statements such as "The
| pandemic will end once everyone is vaccinated" since that
| presumes a LOT.
| _Wintermute wrote:
| You're assuming it's the scientists making these grand
| claims. Unfortunately it's often the case the scientists will
| make some small claim with lots of caveats, a university
| press officer will hype it up, the media will then take that
| and make it into the most attention grabbing headline they
| can.
| netizen-936824 wrote:
| This sorta jives with my observations, but from my
| experience it seems like its the general population
| journalists that mess things up. There's such little
| understanding of these complex topics and then journalists
| try to cram as much info into a small place and pick the
| things that sound most important to them. Detail gets lost
| and importance of some aspects overblown. This happens
| through multiple stages as in a game of telephone from
| original research all the way to average people reading or
| watching the news
| otabdeveloper4 wrote:
| > How The Science tells us the pandemic will end once
| everyone is vaccinated
|
| Fixed it for you.
| samus wrote:
| > headlines such as "The Universe is growing faster than it
| should" or "How science tells us the Pandemic will end once
| everyone is vaccinated".
|
| Such headlines are the hallmark of popular science journals,
| who indeed seem to do damage to the credibility of science by
| riding the clickbait wave.
| fabian2k wrote:
| Those statements were true for the original virus. They are not
| true for the current variant. And we really can't predict what
| new variants can do, we could have guessed that new, more
| transmissible variants are likely to emerge, but we can't
| predict the future.
| refurb wrote:
| So basically anything scientists tell us may or may not be
| true depending on how the future evolves?
|
| Come on man!
| dekhn wrote:
| Yes, this is absolutely the case. Public health leadership
| is flying in the dark about the evolution of the virus.
| anamax wrote:
| > Public health leadership is flying in the dark about
| the evolution of the virus.
|
| And yet, it says that it knows all.
|
| Which reminds me - are eggs good or bad this month?
| epgui wrote:
| I am a scientist: yes.
| Traubenfuchs wrote:
| > Meanwhile, the tragic loss of respect for scientific authority
| around the world
|
| Governments and their figurehead ,,scientists" like Fauci have
| rightfully lost all our trust by contradicting the nonsense and
| lies they spew and moving the goalposts every other day, under
| the weak guise of ,,developing/new knowledge".
| mdp2021 wrote:
| In fact, it's not really "scientists": scientists "search" (put
| together puzzle pieces, check hypotheses), they do not climb on
| pedestals claiming close social relation with The Truth. It's
| political agents looking for excuses.
|
| You appear, with that formulation, to have missed the paragraph
| just above:
|
| > _And scientists have been attacked in new ways and with new
| methods by politicians who are exploiting social media and
| long-tested methods of indoctrination to undermine scientific
| authority on issues ranging from vaccines in the midst of a
| pandemic to the impending devastation of climate change_
|
| In a stub (unfortunately), the author claimed that the role of
| science is under political attack.
|
| Very clearly (in some regions), there as been a devastating
| blow against civilization attempting through narratives for
| propaganda to make of science a fideistic sect, a doctrine -
| its opposite.
| [deleted]
| [deleted]
| zhengiszen wrote:
| Excellent summary of the year 2021
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