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The next frontier in protein design will not be defined by structure alone, but by the capacity to engineer motion as a first-class principle of function. This is because dynamics is where the real biology lives. Foundational work by Karplus, Levitt & Warshel made clear that chemistry cannot be...

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This is how DNA turns coded information into functional proteins - the building blocks of the nanomachines that keep the cells in your body alive. This complex process highlights the sophisticated interconnected systems of Life which must all exist together from the beginning, or Life doesn't happen. First, an RNA molecule is copied from a short segment of DNA. Without the specifically ordered DNA information, RNA cannot form, proteins cannot be built, cells stop working, and life ceases to exist. Life is information first. Once the RNA Molecule is created, it gets ejected from the Polymerase where it was built, and it travels through a complex molecular machine called a Nuclear Pore Complex (NPC), which is an information recognition device that controls the flow of information in and out of a cell's nucleus. The NPC is highly complex - composed of about 500-1,000 protein subunits, derived from a set of about 35 distinct proteins. Without this molecular machine, there is no regulation for what goes in and out of the cell's nucleus, which would lead to catastrophic death for the cell. It must exist for cells to exist. Once the RNA Molecule passes through the NPC, it travels to the Ribosome, a 2-part chemical factory which reads the information on RNA and uses it to construct functional proteins using a specifically sequenced chain of amino acids. Once complete, this protein will then be sent to the section of the cell it belongs to integrate into another molecular machine and do its job. The Ribosome is another highly complex molecular machine - consisting of between 56-80 proteins. Without this molecular machines, proteins cannot be built. Proteins are the building blocks of every cell in every organism on Earth. Without Ribosomes, Life doesn't exist. If you're paying attention, you'll start to realize that Life relies on a highly sophisticated interdependent network of complex machines, which all rely on each other for the function of the system. DNA requires the cell for stability, but the cell requires the proteins for its structure and function, but those proteins require DNA and RNA to be built - it's a circle of necessary interdependence. Systems like this cannot be built by evolutionary processes, which requires that each piece of the process is built by gradual incremental means over lots of time. Without all the pieces there, from the beginning, none of it works. There is only one known source of complex & interdependent informational systems like those we find in life: and that is from Intelligence. Molecular Biology is the best and most obvious evidence of the Intelligent Design in Life.

Divinely Designed

62,517 Aufrufe • vor 6 Monaten

Proof that Life is Intelligently Designed: Proteins. They do everything in your cells that keeps you alive. These microscopic molecules must have been created. Here is why: Proteins are the building blocks of all the little nano-machines that make up your cells. They do all the major work in your body - from creating energy to recycling waste. Proteins are made from amino acids connected into a specific sequence and then folded into a functional shape. You can think of a protein like a paragraph, and amino acids as the individual letters that spell out the words. Here is where it gets interesting... There are just 20 amino acids used in all of Life. Just 20 amino acids. Responsible for ~200 million unique proteins making up tens of thousands of cell types across Life. And scientists are constantly finding new ones. Scientists categorize proteins into Families. Protein Families are groups of proteins that share amino acid sequence similarities. There are ~22,000 Protein Families. Here's the part that screams they are designed... Protein Families have no evolutionary history. Even evolutionist scientists agree - they are absolutely unique. It's been said that proteins are like stars in a galaxy, and families are like galaxies, with vast empty space between them. Evolution is supposed to build by tweaking things that already exist. But no evolutionary history connects fundamentally distinct protein families. Experiments have been done to intentionally evolve one protein family into another. They fail every time. One protein family cannot be evolved into another. They cannot arise through evolution. But the math really makes it impossible... The odds of evolution finding even a single functional protein family is 1 chance in 10^77 possible amino acid sequences. That's a 1 with 77 zeroes. The odds of evolution finding 22,000 distinct protein families? Roughly 1 chance in 10^1,694,000. You don't need to be a mathematician to understand that this is impossible. Evolution works by random mutations tweaking what's already there. But protein families can't evolve from one another. And the math makes it absolutely absurd to believe. Monkeys banging on keyboards will never type out Shakespeare. And random mutations in sequences of amino acids could never create a single functional protein family. There is only one thing we know of that creates functionally specified sequences: Intelligence. Now here is the final cherry on top: Proteins are built by other proteins, assembled into a complex machine to do a job in cells. The assembly instructions for those proteins and the machines are found in DNA. But DNA requires protein machines for replication & repair. So DNA is required to make Proteins... ...but Proteins are required to make DNA *and* more Proteins. You can't have one without the other. They rely on each other. Which means one couldn't have evolved and then waited for the other. They couldn't do anything without each other. They had to be created at the same time to function together. Life was Divinely Designed. Proteins prove it.

Divinely Designed

18,768 Aufrufe • vor 18 Tagen

What seemed like an intractable problem is now possible: To design proteins with a specified nonlinear mechanical response, capturing complex folding and unfolding mechanisms in singe and few-shot computations. We present ForceGen, an end-to-end algorithm for de novo protein generation based on nonlinear mechanical unfolding responses. Rooted in the physics of protein mechanics, this generative strategy provides a powerful way to design new proteins rapidly, including exquisite and rapid predictions about their dynamical behavior. Proteins, like any other mechanical object, respond to forces in peculiar ways. Think of the different response you'd get from pulling on a steel cable versus pulling on a rubber band, or the difference between honey and glass. Now, we can design proteins with a set of desirable mechanical characteristics, with applications from health to sustainable plastics. The key to solving this problem was to integrate a protein language model with denoising diffusion methods, and using accurate atomistic-level physical simulation data to endow the model a first-principles understanding. ForceGen can solve both forward and inverse tasks: In the forward task, we can predict how stable a protein is, how it will unfold and what the forces involved are, all given just the sequence of amino acids. In the inverse task, we can design new proteins that meet complex nonlinear mechanical signature targets. Read the paper, led by LAMM@MIT postdoc Bo Ni, published in Science Advances: Why do we care about the mechanics of proteins? The mechanics of proteins are critical elements of many living systems - as evidenced in many studies of mechanobiology. Through evolution, nature has presented a set of remarkable protein materials with unique mechanical functions like elastins, silks, keratins or collagens that play crucial roles in biology. However, going beyond natural designs to discover proteins that meet specified mechanical properties remains challenging. So far, the only way to do this was to use existing evolutionary concepts or to manually alter proteins. With our new generative model we can directly design proteins to meet complex nonlinear mechanical property-design objectives. ForceGen leverages deep knowledge on protein sequences from a pretrained protein language model and maps mechanical unfolding responses to create proteins. Via full-atom molecular simulations for direct validation from physical and chemical principles, we demonstrate that the designed proteins are de novo, and fulfill the targeted mechanical properties, including unfolding energy and mechanical strength, and a detailed unfolding force-separation curves. ForceGen offers rapid pathways to explore the enormous mechanobiological protein sequence space unconstrained by biological synthesis, to enable the discovery of new protein materials with superior mechanical properties. B. Ni, D.L. Kaplan, M.J. Buehler, ForceGen: End-to-end de novo protein generation based on nonlinear mechanical unfolding responses using a language diffusion model. Sci. Adv. 10, eadl4000 (2024). DOI: 10.1126/sciadv.adl4000 Codes and model weights available Hugging Face: David Kaplan

Markus J. Buehler

47,242 Aufrufe • vor 2 Jahren

This is a Kinesin Molecule. These little molecular machines are commonly referred to as the "workhorse" of the cell, hauling important cargo like organelles, proteins and other cellular structures to their proper location within the cell. Kinesins are very clear & undeniable evidence of the intelligent design in Life. Kinesins are complex molecular machines, made up of 4 total proteins, each between 500-1,300 amino acids in length. If these aa sequences are not perfectly aligned from the beginning, Kinesin never forms, and cellular life would be unable to survive. Here is how they work: When a new protein, organelle, or other cellular structure is created in the Cytosol of the cell, they are constructed with built-in "binding tags," which are like shipping labels that bind to other protein molecules called Adaptor or Scaffold Proteins. These Adaptor/Scaffold Proteins then attach to the Kinesin's tail, which activates them, and then the Kinesin is guided along the microtubule track to its to its final destination. Kinesin walk on self-assembling tracks of other proteins, called microtubules, moving cargo from the inner area of the cell where they are constructed to the outer edges where they function. This is a complex & sophisticated interdependent network of molecular machines, all relying on one another to function properly for the health of the cell. This Intracellular Transportation system MUST be fully functional from the beginning - with all these working parts, or all of it fails, and the cell dies. Without this entire functioning system, Life could not exist. And the Kinesin is the centerpiece to all of it. Experiments have shown that disrupting Kinesin activity has catastrophic consequences. This type of nano-precision is an obvious example of designed engineering. Blind, unguided evolutionary processes cannot plan ahead and create complex informational highways for precision transportation. The proposed evolutionary explanation is simply "co-option." A nebulous term which basically amounts to, "We don't know how it evolved, but it must have evolved from some other thing that was similar in the past." No observational data supports evolutionary co-option. It's absurd to believe any part of this was built by blind chance. Everything in the cell points to Intelligent Design.

Divinely Designed

15,877 Aufrufe • vor 6 Monaten

Elon Musk just described a future where money does not exist. Not reformed. Not redistributed. Gone. Musk: “I think things will just be free in the future. If you’ve got an AI robotics economy that is anywhere close to a million times the size of the current Earth economy, literally any need you possibly want can be met.” Forget the sci-fi framing. Listen to what he is actually saying. The entire structure of human civilization runs on a single variable. You need something you cannot freely access. That gap is not a flaw in the system. It is the system. Your employer does not pay you because your work has value. Your employer pays you because you have no choice but to show up. Your government does not protect you out of principle. It maintains order because your dependency on the economy makes you governable. Scarcity is not a natural condition. It is the most successful control structure ever built. Musk: “If you can think of it, you can have it.” Now ask what happens when that structure collapses. A population that does not need a paycheck cannot be managed by one. A population that does not need credit cannot be disciplined by debt. A population that has everything has no reason to comply with anything. This is not a conversation about free goods. This is a conversation about the largest redistribution of leverage in recorded history. But there is a second collapse no one is talking about. Most people have built their entire identity around the constraint. The career they resent is the structure that tells them where to be every morning. The bills they complain about are the exact reason they never had to ask a harder question. Musk: “There actually isn’t money in the future and there’s abundance for everyone.” When the constraint disappears, so does the excuse. The crisis of the coming century will not be material. It will be millions of people standing in total freedom. Discovering they have no idea who they are without the struggle. Every barrier will be gone. And you will finally have to face the one thing scarcity has been protecting you from your entire life. Yourself.

Dustin

41,736 Aufrufe • vor 2 Monaten

David Chalmers on why consciousness is science's greatest unsolved problem: Science has mapped subatomic particles, distant stars, the chemistry of life yet it remains almost completely silent on the one thing we know most directly: our own conscious experience. In a rare early interview, philosopher David Chalmers explains why: "Consciousness is at once the most familiar thing in the world and the most mysterious. Consciousness is what we start with when it comes to knowing the world. I know that I exist. I know that I'm conscious. Everything else is secondary." And yet, despite this intimacy, consciousness sticks out like a sore thumb in the scientific picture. Chalmers points to a deep irony: science has made extraordinary progress on phenomena that are extraordinarily remote: subatomic particles, distant galaxies, the molecular machinery of biology while making almost no progress on the one thing closest to us. Why? Because science, by design, eliminates the subjective. "To do proper science, you have to be objective. You have to eliminate anything subjective from the picture." He uses heat as the perfect example. Physics gives us a complete account of heat molecules in motion, energy transfer, temperature gradients. It explains every objective aspect of the phenomenon. But it never explains what hotness actually feels like. "Science doesn't actually give a theory of the conscious feeling of hotness." This is what Chalmers calls the Hard Problem of Consciousness. You can trace every neural signal from your heat sensor along your nerves into your brain and still have explained nothing about the subjective experience of feeling warm. As interviewer Jeffrey Mishlove puts it: you can't even do science without a conscious mind to observe, interpret, and make meaning of data. Consciousness is the precondition for science itself and yet science has no framework to account for it. Chalmers' conclusion is striking: The methods of science may need to be expanded. Consciousness might not be something science explains away. It might be something science has to learn to start with.

Mateus — eu/acc 🇪🇺

31,628 Aufrufe • vor 3 Monaten

Martha Nussbaum on why Aristotle believed you are not made of matter. In a 1987 interview on the Great Philosophers, philosopher Martha Nussbaum lays out Aristotle's three-part case against material reductionism, the idea that what you fundamentally are is just the stuff you're made of. His argument is more intuitive than it might sound. First: your matter is always changing. "Matter is always going in and out; it's always changing and of course you do change your material constituents very, very often without ceasing to be yourself." Your cells replace themselves. Your body is not the same collection of atoms it was years ago. And yet you are still you. If your identity were your matter, it would vanish and return constantly. But it doesn't. Something persists that isn't the material. Second: what makes a thing that thing is its function, not its parts. Aristotle uses the example of a ship. Replace some of its planks so long as "its functional structure remains the same, we could always replace bits of the matter without having a different thing in our hands." It's still the same ship. The same logic applies to you. Swap out the components, preserve the structure and function and the identity remains intact. This suggests identity lives in the organisation, not the raw material. Third: matter alone is too vague to define anything. This is perhaps his sharpest point. "Matter is just a lump or heap of stuff and so we couldn't say you are some stuff or other; it's only when we've identified the structure that the stuff constitutes that we can even go on to say something intelligent about the stuff itself." In other words: matter, by itself, tells you nothing. It's formless. You need structure form, function, organisation before you can even begin to describe what a thing is. The deeper implication Aristotle is reaching toward: what makes you you isn't a quantity of carbon and water. It's a pattern. A functional whole. A form that persists through constant material flux. Which raises the question if identity isn't located in matter, where exactly does it live?

Mateus — eu/acc 🇪🇺

69,935 Aufrufe • vor 3 Monaten

I've become a missionary with one message. Every time I meet a young person, the same words: have children, get married, build a family. I did not decide on this calling. It overtook me. And it overtook me for a single reason. I had no idea. I genuinely did not understand how much joy, how much meaning, how much sheer beauty pours out of a child until I was holding one of my own and felt the floor of my life drop into something deeper than I knew was there. I grew up white, affluent, secular, comfortable, and insulated. That world does not put babies in front of you. None of my friends were starting families. Out of my whole circle, almost no one has a big one. We were not formed by the presence of children. We were formed by their absence, by the strange quiet of homes built for two careers and no cradle. And a person believes what his world shows him. So we believed. What we believed was a lie. It is a lie with an author, and that the author is the enemy of joy himself. It is the gospel of the world, and its commandment is wait. Wait until you are older. Wait until the career is built and the savings are stacked and the twenties are properly spent. Enjoy your freedom. You are not ready. It does not arrive sounding like temptation. It arrives sounding like wisdom, like prudence, like the responsible thing, and that is exactly why it works. The most effective lies are the ones that wear the face of virtue. And the maddening thing is that it collapses from every angle at once. It is not rooted in biology, because the body is made for this work precisely in the years we are told to postpone it. The flesh keeps a calendar the culture pretends not to see. And it is not rooted in theology either. You will not find this deferral anywhere in the Christian imagination, in any of the fathers, in any of the scriptures. So choose whatever lens you like. Take the cold secular measure or the ancient sacred one. By either light the counsel is rotten. It is bad for the body and bad for the soul and bad for the society downstream of both. This is why I have come to see it as one of the central tragedies of my generation. Every age carries its own wound. The Great Depression was a depression of bread, a scarcity in the world of matter, hunger you could measure. Ours is a depression of a different order. It is a famine of the spirit in the middle of abundance. We have more than any people who ever lived and we are starving in a way our ancestors would not recognize, because the thing we are refusing cannot be bought and cannot be banked. The ones most made to give and receive this love are quietly declining it. They are walking away from the one inheritance that actually compounds, and the cruelest part is that they do not feel the loss as loss. You cannot grieve what you were taught not to want. That is the deepest cut of it. The lie does not only steal the thing. It steals the capacity to know the thing was stolen. A man can spend his whole life on the far side of a door he never knew was a door, mistaking the wall for the edge of the world. Because this beauty is not ordinary beauty. It is not the pleasure of a good meal or a clear morning. It is participation in something that comes down from above, the same generative love that spoke everything out of nothing and called it good. To make a person, to be undone and remade by loving that person more than your own life, is to be drawn for a moment inside the very act that holds the cosmos together. A child does not merely add to your life. A child reorders the soul. It teaches you what you are by asking everything of you, and you discover, kneeling there exhausted at three in the morning, that you had a capacity for self gift you never suspected, a depth in yourself you had no other way to reach. In the Gospel of John, on the last night, Jesus prays, these things I have spoken to you that my joy may be in you, and that your joy may be complete. And I have come to understand why family is the road into that fullness, why it is not one path among many but the one most fitted to the shape of the promise. Consider who is praying. Christ does not come to us as a lone figure dropped out of the sky. He comes out of a family older than the world, the eternal communion of Father and Son, the love between them so total and so alive that theologians dared to call it a third person. Before there was anything, there was a family. The deepest fact about reality is not a force or a law or a void. It is a household. It is begetting and being begotten, giving and receiving, a Father who is only a Father because there is a Son. So when Jesus speaks of joy made complete, he is not pointing away from family toward something higher. He is pointing toward the very thing he came from, the life he has known from eternity and came to share. His joy is the joy of belonging utterly to a Father and pouring himself out for those he loves. When you marry, when you bring a child into the world, when you wear yourself down in the small unseen labors of a home, you are not stepping outside that divine life. You are stepping into a small image of it. Your family is a created echo of an uncreated one. The love you give your child rhymes with the love the Father has for the Son. The exhaustion, the tenderness, the way a parent would tear the sky open to protect a sleeping infant, all of it is the heavens pressed faintly into flesh, the eternal household leaving its fingerprint on yours. That is why the joy is not merely added to family but completed in it. We were made in the image of a God who is, at his very root, relation and gift and generation. To found a family is to do the most Godlike thing a creature can do, to participate from below in the begetting that God does from all eternity. Your home becomes a window. Through it, dimly and imperfectly, you glimpse the country you came from and are going to. And now a word for the young people reading this, the ones who do not yet have children. I want to tell you what it is like from where I stand. When I am out somewhere, a restaurant, anywhere, and a large family comes through the door, the noise and the chaos and the small bodies of them, something happens in me on two levels at once. The first is joy. A pure gladness at the sight, the way you feel watching something good and alive. But underneath it, almost in the same instant, a sadness reaches up and takes hold of my heart. Because I know now, at my age, after my own years of waiting, that I will never have that. I will never know the particular fruit of a family that large, the fullness of that table, the weight of all those lives gathered under one roof. The door to it has quietly closed, and I felt it close. And I am telling you plainly, because I love you and have no reason to lie to you: you will feel this too. You will. The day will come when you see what you passed up, and you will recognize the ache for what it is, and it will be too late to answer it. So please, learn from a man who got it wrong. Let my regret be worth something by becoming your wisdom. Do not wait yourself into a grief you cannot undo. Choose now, while the door is open, so that you may step into a joy that does not end.

Kirk Rollins

77,958 Aufrufe • vor 1 Monat