If we need AlphaFold to figure out protein folding, how likely is protein folding to be a product of mere chance?

6 Replies to “If we need AlphaFold to figure out protein folding, how likely is protein folding to be a product of mere chance?”

1. 1
   martin_r says:

   October 28, 2020 at 2:06 am

   Protein folding – an ultimate proof of cell design (among others)
2. 2
   ET says:

   October 28, 2020 at 7:49 am

   There are too many proteins that require chaperones to fold properly to say it was chance.
3. 3
   bornagain77 says:

   October 28, 2020 at 3:36 pm

   ET mentions chaperones. Here are a few notes along that line:

   Nature Review Article Yields Unpleasant Data For Darwinism – August 2011
   Excerpt: The number of possible shapes that a protein can fold into is very high and folding reactions are very complex, involving the co-operation of many weak, non-covalent interactions. A high percentage of proteins do not fold automatically into the required shape and are at risk of aberrant folding and aggregation. As the abstract to this paper states: “To avoid these dangers, cells invest in a complex network of molecular chaperones, which are ingenious mechanisms to prevent aggregation and promote efficient folding.”
   http://www.uncommondescent.com.....darwinism/

   Body Wonders at the Cellular Level – September 9, 2014
   Excerpt: Two scientists (Kazutoshi Mori and Peter Walter) won the Lasker Prize,, for discovering how cellular machines in the endoplasmic reticulum (are regulated to correct misfolded) proteins.,,
   One of the researchers, Kazutoshi Mori, described his feelings at the wonder of discovery:
   “We wanted to find the molecular machinery that allows one component of the cell to talk to another. There was virtually nothing known about what was taking place.,,,
   The deeper we dove, however, the more complex it became and the more beautiful it became.…
   We discovered machinery by which the cell has the capacity to fold the protein properly and pathway by which this happened. We mapped the components of the pathway and everything turned out to be more exciting than we could have hoped for.”
   http://crev.info/2014/09/body-.....lar-level/

   Protein folding: Much more intricate than we thought:
   Scientists are still uncovering all the players that help keep proteins folded inside cells—and all the ways the process can go wrong – by Sarah Everts – JULY 31, 2017
   Excerpt: researchers have discovered that protein folding is much more than just a perfunctory, fleeting performance before the real biology begins. Protein folding is a constantly ongoing, complicated biological opera itself, with a huge cast of performers, an intricate plot, and dramatic denouements when things go awry.
   In the packed, busy confines of a living cell, hundreds of chaperone proteins vigilantly monitor and control protein folding. From the moment proteins are generated in and then exit the ribosome until their demise by degradation, chaperones act like helicopter parents, jumping in at the first signs of bad behavior to nip misfolding in the bud or to sequester problematically folded proteins before their aggregation causes disease. “People often mistakenly think that proteins are free to live out their lives in a cell,” says Stanford University’s Judith Frydman. “Instead, for many proteins, existence in a cell is more like life in a totalitarian state. They are never really released from the clutches of the chaperones to find their independent way” inside the cell.
   As it becomes increasingly clear that folding is not a once-in-a-lifetime event for proteins but instead a part of day-to-day life in the cell,
   https://cen.acs.org/content/cen/articles/95/i31/Protein-folding-Much-intricate-thought.html

   Cell Machinery Untangles Misfolded Proteins – April 2, 2013
   Excerpt: biologist Helen R. Saibil, provides a model diagram of this “highly dynamic” machine and descriptions of what the parts do. There are channels, toggles, linkers, mobile lids, and dockers. One of the primary parts looks like a stack of 3-tiered rings with a channel down the middle. The other part looks a little like Pac-man, biting down on a “hot spot” on the side of the rings, accompanied by other moving parts. Each of the primary parts is further composed of several protein domains. Multiple ATP “energy pellets” power the operation at three locations.
   The cell first has to identify the misfolded aggregate, find a loose end, and feed it into a slot on the side-mounted machine. The docking point acts as a regulator that can reprogram the side-mounted machine according to the stage of the operation. Once threaded into the right position, the loose end is fed into the central channel of the three-tiered machine, so that untangling can proceed. The untangled polypeptide exiting the central channel can then be refolded by other chaperone machines at the ready.?Only dim details of this operation are understood so far. The “mechanism” by which the strand is “handed over” from one domain to the other is “unclear,” Saibil writes. It’s also not clear how the tangled mess of peptide pictured in the model diagram can avoid snags as it passes through the machinery. Yet it works. Rightly, Dr. Saibil praises “the remarkable ability of cells to reverse protein aggregation.”
   http://www.evolutionnews.org/2.....70411.html

   (How do) Chaperone Proteins Know (how to fold other proteins)? – September 2012
   Excerpt: Here are some of the neat features of Trigger Factor:
   *Trigger Factor actually constrains protein folding more than the ribosome does. It doesn’t just “get in the way” like the ribosome. It also regulates the folding.
   *Trigger Factor’s function is specific to the particular region of the amino acid chain. It does not just perform one function no matter what the composition of the amino acid chain. It changes based on the region of the chain it is working with.
   *Trigger Factor also changes its activity based on where the protein is in the translation process.
   *Trigger Factor’s process depends on how the amino acid chain is bound to the ribosome, and can even unfold parts of the chain that were misfolded in the translation process.
   An additional factor that regulates when amino acid chains fold into proteins is its distance from the ribosome (the place where the amino acid chain is made). The closer the chain is to the ribosome, the less room it has to fold into a three-dimensional protein. Trigger Factor works with this spatial hindrance, making an interesting and complex regulation system.
   Trigger Factor is only called into the game once the amino acid chain is a certain length (around 100 amino acids long) and when the chain has certain features, such as hydrophobicity. As the authors state it, Trigger Factor keeps the protein from folding into its three-dimensional structure until the amino acid chain has all of the information it needs to fold properly:
   In summary, we show that the ribosome and TF each uniquely affect the folding landscape of nascent polypeptides to prevent or reverse early misfolds as long as important folding information is still missing and the nascent chain is not released from the ribosome.
   So we have a protein that is able to perform various functions that inhibit or slow protein folding until the amino acid has the right chemical information for folding to occur.
   This does not solve the riddle about proteins being made from proteins (otherwise known as the chicken-and-the-egg problem). It actually adds another twist to the riddle: How does one protein know how much information a completely different protein needs to fold into a three dimensional structure? How does a protein evolve the ability to “know” how to respond to specific translational circumstances as Trigger Factor does?
   http://www.evolutionnews.org/2.....63951.html
4. 4
   bornagain77 says:

   October 28, 2020 at 4:18 pm

   As to this comment from the OP:

   AlphaFold beat all the humans in 2019 (in figuring out how to fold proteins) just because it could handle the calculations. That’s what computers do.

   As to the some of the complexity involved in figuring out, i.e. ‘computing’, protein folding.

   ‘Traveling salesman problems’ are notorious for keeping supercomputers busy for days, and are are considered ‘Just about the meanest problems you can set a computer (on)’. And “Solving the traveling-salesman problem is a little like finding the most stable folded shape of a protein’s chain-like molecular structure — in which the number of ‘cities’ can run to hundreds or even thousands.”

   Tiny brained bees solve a complex mathematical problem – 25 October 2010
   Excerpt: “In nature, bees have to link hundreds of flowers in a way that minimises travel distance, and then reliably find their way home – not a trivial feat if you have a brain the size of a pinhead! Indeed such travelling salesmen problems keep supercomputers busy for days. Studying how bee brains solve such challenging tasks might allow us to identify the minimal neural circuitry required for complex problem solving.”
   http://www.qmul.ac.uk/media/ne.....38864.html

   DNA computer helps traveling salesman – Philip Ball – 2000
   Excerpt: Just about the meanest problems you can set a computer belong to the class called ‘NP-complete’. The number of possible answers to these conundrums, and so the time required to find the correct solution, increases exponentially as the problem is scaled up in size. A famous example is the ‘travelling salesman’ puzzle, which involves finding the shortest route connecting all of a certain number of cities.,,,
   Solving the traveling-salesman problem is a little like finding the most stable folded shape of a protein’s chain-like molecular structure — in which the number of ‘cities’ can run to hundreds or even thousands.
   http://www.nature.com/news/200.....13-10.html

   Moreover, if protein folding occurred by random processes, (as would be presupposed under Darwinian presuppositions), then a “random search could never find the final folded conformation of,,, even a small (say, 100 residue) unfolded protein,,, during the lifetime of the physical universe.”

   The Humpty-Dumpty Effect: A Revolutionary Paper with Far-Reaching Implications – Paul Nelson – October 23, 2012
   Excerpt: Anyone who has studied the protein folding problem will have met the famous Levinthal paradox, formulated in 1969 by the molecular biologist Cyrus Levinthal. Put simply, the Levinthal paradox states that when one calculates the number of possible topological (rotational) configurations for the amino acids in even a small (say, 100 residue) unfolded protein, random search could never find the final folded conformation of that same protein during the lifetime of the physical universe. Therefore, concluded Levinthal, given that proteins obviously do fold, they are doing so, not by random search, but by following favored pathways. The challenge of the protein folding problem is to learn what those pathways are.
   http://www.evolutionnews.org/2.....65521.html

   Yet in real life, a protein folds into its shape in the microseconds to nanoseconds range, (not the billions of years range)

   Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation – December 5, 2000
   https://www.pnas.org/content/97/25/13518

   Of related interest, quantum computers excel at solving ‘traveling-salesman problems’,,,

   Speed Test of Quantum Versus Conventional Computing: Quantum Computer Wins – May 8, 2013
   Excerpt: quantum computing is, “in some cases, really, really fast.”
   McGeoch says the calculations the D-Wave excels at involve a specific combinatorial optimization problem, comparable in difficulty to the more famous “travelling salesperson” problem that’s been a foundation of theoretical computing for decades.,,,
   “This type of computer is not intended for surfing the internet, but it does solve this narrow but important type of problem really, really fast,” McGeoch says. “There are degrees of what it can do. If you want it to solve the exact problem it’s built to solve, at the problem sizes I tested, it’s thousands of times faster than anything I’m aware of. If you want it to solve more general problems of that size, I would say it competes — it does as well as some of the best things I’ve looked at. At this point it’s merely above average but shows a promising scaling trajectory.”
   http://www.sciencedaily.com/re.....122828.htm

   And the following study found that, “if this process (of protein folding) were a quantum one, the shape could change by quantum transition, meaning that the protein could ‘jump’ from one shape to another without necessarily forming the shapes in between.,,,

   Physicists Discover Quantum Law of Protein Folding – February 22, 2011
   Quantum mechanics finally explains why protein folding depends on temperature in such a strange way.
   Excerpt: First, a little background on protein folding. Proteins are long chains of amino acids that become biologically active only when they fold into specific, highly complex shapes. The puzzle is how proteins do this so quickly when they have so many possible configurations to choose from.
   To put this in perspective, a relatively small protein of only 100 amino acids can take some 10^100 different configurations. If it tried these shapes at the rate of 100 billion a second, it would take longer than the age of the universe to find the correct one. Just how these molecules do the job in nanoseconds, nobody knows.,,,
   Today, Luo and Lo say these curves can be easily explained if the process of folding is a quantum affair. By conventional thinking, a chain of amino acids can only change from one shape to another by mechanically passing through various shapes in between.
   But Luo and Lo say that if this process were a quantum one, the shape could change by quantum transition, meaning that the protein could ‘jump’ from one shape to another without necessarily forming the shapes in between.,,,
   Their astonishing result is that this quantum transition model fits the folding curves of 15 different proteins and even explains the difference in folding and unfolding rates of the same proteins.
   That’s a significant breakthrough. Luo and Lo’s equations amount to the first universal laws of protein folding. That’s the equivalent in biology to something like the thermodynamic laws in physics.
   http://www.technologyreview.co.....f-protein/

   Moreover, it is now found that proteins do indeed belong to the world of quantum physics, not to the world of classical physics, (as is presupposed within the framework of Darwinian materialism),

   The following 2015 article experimentally confirmed that proteins are indeed based on quantum principles. More specifically, the following study observed that quantum processes “concentrate all of the vibrational energy in a biological protein into its lowest-frequency vibrational mode.”

   Quantum coherent-like state observed in a biological protein for the first time – October 13, 2015
   Excerpt: If you take certain atoms and make them almost as cold as they possibly can be, the atoms will fuse into a collective low-energy quantum state called a Bose-Einstein condensate. In 1968 physicist Herbert Fröhlich predicted that a similar process at a much higher temperature could concentrate all of the vibrational energy in a biological protein into its lowest-frequency vibrational mode. Now scientists in Sweden and Germany have the first experimental evidence of such so-called Fröhlich condensation (in proteins).,,,
   The real-world support for Fröhlich’s theory (for proteins) took so long to obtain because of the technical challenges of the experiment, Katona said.
   http://phys.org/news/2015-10-q.....otein.html

   As well, in the following 2006 article entitled ‘Classical and Quantum Information Channels in Protein Chain’ it was stated that, “On the basis of force constants, displacements of each atom in peptide plane, and time of action we found that the value of the peptide plane action is close to the Planck constant. This indicates that peptide plane from the energy viewpoint possesses synergetic classical/quantum properties.”

   Classical and Quantum Information Channels in Protein Chain – Dj. Koruga, A. Tomi?, Z. Ratkaj, L. Matija – 2006
   Abstract: Investigation of the properties of peptide plane in protein chain from both classical and quantum approach is presented. We calculated interatomic force constants for peptide plane and hydrogen bonds between peptide planes in protein chain. On the basis of force constants, displacements of each atom in peptide plane, and time of action we found that the value of the peptide plane action is close to the Planck constant. This indicates that peptide plane from the energy viewpoint possesses synergetic classical/quantum properties. Consideration of peptide planes in protein chain from information viewpoint also shows that protein chain possesses classical and quantum properties. So, it appears that protein chain behaves as a triple dual system: (1) structural – amino acids and peptide planes, (2) energy – classical and quantum state, and (3) information – classical and quantum coding. Based on experimental facts of protein chain, we proposed from the structure-energy-information viewpoint its synergetic code system.
   http://www.scientific.net/MSF.518.491
5. 5
   bornagain77 says:

   October 28, 2020 at 4:18 pm

   And in the following more recent 2015 paper entitled, “Quantum criticality in a wide range of important biomolecules” it was found that “Most of the molecules taking part actively in biochemical processes are tuned exactly to the transition point and are critical conductors,” and the researchers further commented that “finding even one (biomolecule) that is in the quantum critical state by accident is mind-bogglingly small and, to all intents and purposes, impossible.,, of the order of 10^-50 of possible small biomolecules and even less for proteins,”,,,

   Quantum criticality in a wide range of important biomolecules – Mar. 6, 2015
   Excerpt: “Most of the molecules taking part actively in biochemical processes are tuned exactly to the transition point and are critical conductors,” they say.
   That’s a discovery that is as important as it is unexpected. “These findings suggest an entirely new and universal mechanism of conductance in biology very different from the one used in electrical circuits.”
   The permutations of possible energy levels of biomolecules is huge so the possibility of finding even one (biomolecule) that is in the quantum critical state by accident is mind-bogglingly small and, to all intents and purposes, impossible.,, of the order of 10^-50 of possible small biomolecules and even less for proteins,”,,,
   “what exactly is the advantage that criticality confers?”
   https://medium.com/the-physics-arxiv-blog/the-origin-of-life-and-the-hidden-role-of-quantum-criticality-ca4707924552

   And as the follow up article further stated, “There is no obvious evolutionary reason why a protein should evolve toward a quantum-critical state, and there is no chance at all that the state could occur randomly.,,,”

   Quantum Critical Proteins – Stuart Lindsay – Professor of Physics and Chemistry at Arizona State University – 2018
   Excerpt: The difficulty with this proposal lies in its improbability. Only an infinitesimal density of random states exists near the critical point.,,
   Gábor Vattay et al. recently examined a number of proteins and conducting and insulating polymers.14 The distribution for the insulators and conductors were as expected, but the functional proteins all fell on the quantum-critical distribution. Such a result cannot be a consequence of chance.,,,
   WHAT OF quantum criticality? Vattay et al. carried out electronic structure calculations for the very large protein used in our work. They found that the distribution of energy-level spacings fell on exactly the quantum-critical distribution, implying that this protein is also quantum critical. There is no obvious evolutionary reason why a protein should evolve toward a quantum-critical state, and there is no chance at all that the state could occur randomly.,,,
   http://inference-review.com/ar.....l-proteins
   Gábor Vattay et al., “Quantum Criticality at the Origin of Life,” Journal of Physics: Conference Series 626 (2015);
   Gábor Vattay, Stuart Kauffman, and Samuli Niiranen, “Quantum Biology on the Edge of Quantum Chaos,” PLOS One 9, no. 3 (2014)

   The interesting thing about finding quantum entanglement to be ubiquitous within life is that quantum entanglement is a ‘non-local’, beyond space and time, effect that requires a ‘beyond space and time cause’ in order to explain it,

   Looking beyond space and time to cope with quantum theory – 29 October 2012
   Excerpt: “Our result gives weight to the idea that quantum correlations somehow arise from outside spacetime, in the sense that no story in space and time can describe them,”
   http://www.quantumlah.org/high.....uences.php

   Moreover, quantum information is also conserved, which means that it cannot be created nor destroyed. As the following article states, In the classical world, information can be copied and deleted at will. In the quantum world, however, the conservation of quantum information means that information cannot be created nor destroyed.

   Quantum no-hiding theorem experimentally confirmed for first time – 2011
   Excerpt: In the classical world, information can be copied and deleted at will. In the quantum world, however, the conservation of quantum information means that information cannot be created nor destroyed. This concept stems from two fundamental theorems of quantum mechanics: the no-cloning theorem and the no-deleting theorem. A third and related theorem, called the no-hiding theorem, addresses information loss in the quantum world. According to the no-hiding theorem, if information is missing from one system (which may happen when the system interacts with the environment), then the information is simply residing somewhere else in the Universe; in other words, the missing information cannot be hidden in the correlations between a system and its environment.
   http://www.physorg.com/news/20.....tally.html

   The implication of finding ‘non-local’, beyond space and time, and ‘conserved’, quantum information in molecular biology on such a massive scale, in every important biomolecule in our bodies, is fairly, and pleasantly, obvious.
   That pleasant implication, of course, being the fact that we now have very strong empirical evidence suggesting that we do indeed have an eternal soul that is capable of living beyond the death of our material bodies. As Stuart Hameroff states in the following article, the quantum information,,, isn’t destroyed. It can’t be destroyed.,,, it’s possible that this quantum information can exist outside the body. Perhaps indefinitely as a soul.”

   Leading Scientists Say Consciousness Cannot Die It Goes Back To The Universe – Oct. 19, 2017 – Spiritual
   Excerpt: “Let’s say the heart stops beating. The blood stops flowing. The microtubules lose their quantum state. But the quantum information, which is in the microtubules, isn’t destroyed. It can’t be destroyed. It just distributes and dissipates to the universe at large. If a patient is resuscitated, revived, this quantum information can go back into the microtubules and the patient says, “I had a near death experience. I saw a white light. I saw a tunnel. I saw my dead relatives.,,” Now if they’re not revived and the patient dies, then it’s possible that this quantum information can exist outside the body. Perhaps indefinitely as a soul.”
   – Stuart Hameroff – Quantum Entangled Consciousness – Life After Death – video (5:00 minute mark)
   https://www.disclose.tv/leading-scientists-say-consciousness-cannot-die-it-goes-back-to-the-universe-315604

   Verse:

   Mark 8:37
   Is anything worth more than your soul?
6. 6
   ET says:

   October 28, 2020 at 6:40 pm

   Even so-called synonymous mutations, mutations in the coding sequence that still codes for the same amino acid, can cause problems. That’s because not all tRNAs are equally represented. And if that leads to a delay in having the proper tRNA get to the ribosome the resulting protein starts folding, prematurely, which causes problems.

   Prions are an example of heredity by contact. The infecting protein alters the shape of other proteins just by contact. That alteration leas to all kinds of problems and then death.