[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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