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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...

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Markus J. Buehler

24,628 subscribers

47,269 次观看 • 2 年前 •via X (Twitter)

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10 条评论

The Guy 的头像
The Guy2 年前

I can imagine someone setting out with a dictionary of all the major cancer causing mutations to find the protein changes they lead to then reverse engineering a "fixer" protein that either marks those cells for destruction or repairs the malfunctioning protein.

Ella Marushchenko 的头像
Ella Marushchenko2 年前

@tamjeeds Congratulations on this fascinating breakthrough! Could ForceGen fast-track the development of self-repairing biomaterials?

Sohm Music 的头像
Sohm Music2 年前

This absolutely has to take the cake, best discovery of the year so far!

Markus Rauhalahti 的头像
Markus Rauhalahti2 年前

Beautiful work! Huge fan of your/group's curiosity towards frameworks and methods, from category theory to the recent LLM explorations. Looking forward to reading this properly and testing it out, thanks for sharing the code and weights!

Markus J. Buehler 的头像
Markus J. Buehler2 年前

Thank you @MRauhalahti !

Gioele Zardini 的头像
Gioele Zardini2 年前

This is amazing Markus, looking forward to discovering more!

Brian Timko Laboratory 的头像
Brian Timko Laboratory2 年前

@KaplanLab_Tufts Very cool!

Jugal 的头像
Jugal2 年前

Congratulations!!

Jason Liu 的头像
Jason Liu2 年前

Congrats! This looks super cool! Did you mean 'single' in "...mechanisms in singe and few-shot computations..." (paragraph 1)?

Ⓜⓐⓡⓖⓘⓝ ⓒⓐⓛⓛ 的头像
Ⓜⓐⓡⓖⓘⓝ ⓒⓐⓛⓛ2 年前

Nice work, similar to AFM.

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We're thrilled to present ESM3 in Science Magazine. ESM3 is a generative language model that reasons over the three fundamental properties of proteins: sequence, structure, and function. Today we're making ESM3 available free to researchers worldwide via the public beta of an API for biological intelligence. Trained with over a trillion teraflops of compute, this is the first time a model of this scale has been trained for biology, pushing the frontier of AI for biological discovery and engineering. ESM3 learns to represent the immense complexity of protein biology, learning from billions of natural proteins. From this training it developed the capability to design proteins, responding to complex prompts combining atomic level details and high level instructions to generate new proteins. ESM3 can explore protein space far beyond natural evolution. We prompted ESM3 to generate a fluorescent protein at a far distance from any known fluorescent proteins, searching an unknown region of protein space, to discover a new fluorescent protein. We estimate this is equivalent to simulating five hundred million years of evolution.
1:31

We're thrilled to present ESM3 in Science Magazine. ESM3 is a generative language model that reasons over the three fundamental properties of proteins: sequence, structure, and function. Today we're making ESM3 available free to researchers worldwide via the public beta of an API for biological intelligence. Trained with over a trillion teraflops of compute, this is the first time a model of this scale has been trained for biology, pushing the frontier of AI for biological discovery and engineering. ESM3 learns to represent the immense complexity of protein biology, learning from billions of natural proteins. From this training it developed the capability to design proteins, responding to complex prompts combining atomic level details and high level instructions to generate new proteins. ESM3 can explore protein space far beyond natural evolution. We prompted ESM3 to generate a fluorescent protein at a far distance from any known fluorescent proteins, searching an unknown region of protein space, to discover a new fluorescent protein. We estimate this is equivalent to simulating five hundred million years of evolution.

Alex Rives

227,542 次观看 • 1 年前

Can Claude Code design proteins? We're just about to release our wet lab API + SDK so we made a quick demo to test how agents can interact with protein design models and submit the proteins to our lab for testing. This closes the loop between the computational design and the experiment validation We queued up a bunch of agent-designed proteins for wet lab validation, will release the results in a couple weeks on Proteinbase
1:15

Can Claude Code design proteins? We're just about to release our wet lab API + SDK so we made a quick demo to test how agents can interact with protein design models and submit the proteins to our lab for testing. This closes the loop between the computational design and the experiment validation We queued up a bunch of agent-designed proteins for wet lab validation, will release the results in a couple weeks on Proteinbase

Julian Englert

81,792 次观看 • 8 个月前

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.
0:38

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

18,886 次观看 • 2 个月前

NEW EPISODE of HARD DRUGS! AlphaFold, ProteinMPNN and other AI tools are transforming biology and drug design. But how do they work? What can’t they do (yet)? And can we use them to make a vaccine against Strep A for the very first time? In this episode, Jacob and I talk about hacking proteins with AI. 03:21 What makes proteins cool 05:29 Can we make a vaccine against Strep A? 10:12 Proteins in nature aren’t enough, and we can improve them with AI 21:12 ProteinMPNN and AlphaFold are transforming drug design 29:52 A short history of protein structure prediction from physical models to deep learning 34:48 Using AI to design a Strep A vaccine 39:27 Validating an AI-designed Strep A vaccine 43:09 Recent AI protein breakthroughs 49:30 Why we don’t already have a Strep A vaccine and the future of optimizing protein drugs
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NEW EPISODE of HARD DRUGS! AlphaFold, ProteinMPNN and other AI tools are transforming biology and drug design. But how do they work? What can’t they do (yet)? And can we use them to make a vaccine against Strep A for the very first time? In this episode, Jacob and I talk about hacking proteins with AI. 03:21 What makes proteins cool 05:29 Can we make a vaccine against Strep A? 10:12 Proteins in nature aren’t enough, and we can improve them with AI 21:12 ProteinMPNN and AlphaFold are transforming drug design 29:52 A short history of protein structure prediction from physical models to deep learning 34:48 Using AI to design a Strep A vaccine 39:27 Validating an AI-designed Strep A vaccine 43:09 Recent AI protein breakthroughs 49:30 Why we don’t already have a Strep A vaccine and the future of optimizing protein drugs

Saloni

72,565 次观看 • 11 个月前

Proteins, the building blocks of all cells, prove Life is Intelligently designed. I'll prove it to you using an analogy. Look at the letters that make up these sentences. They are arranged into a specific pattern that gives the final arrangement functional significance. Letters don't convey any real meaning by themselves - it's not until they're arranged into a sentence that function arises. Proteins are very similar - they achieve functional significance in cells via specifically arranged amino acid sequences. Just as a single letter doesn't do anything by itself, a single amino acid is useless outside a full protein sequence. Evolution is supposed to build new proteins step by step, one amino acid at a time. But think about this: A Is that a meaningful sentence? A B How about that? A BALL BOUNCES. There we go. See, building the sentence one letter at a time provides no functional benefit - it's not until we have the full sequence that function emerges. It's the same with proteins. ...which means evolution can't build them one step at a time. They are all or nothing sequences that requires specific arrangements to be known and created immediately, or they don't function. Evolutionists will argue novel proteins can be evolved from already existing functional proteins. So they simply grant themselves the existence of proteins and claim random mutations can build new ones. Wrong again. There is only about 1 single functional protein fold - the shape an amino acid sequence makes when it becomes a functional protein - in about 10⁷⁷ possible amino acid sequences. That's a 10 with 77 zeroes. Those odds are overwhelmingly prohibitive. Tinkering with amino acid sequences destroys function after not too long, just like randomly changing letters in a word would destroy its meaning. Evolution cannot build novel proteins. No evidence exists showing how it can be done. Proteins exhibit what is called 'specified complexity.' That is, a complex arrangement that is enormously unlikely, unable to be explained by any repeatable pattern, and whose specifity grants function. Natural processes have never been observed to be able to create specified complexity. Only one cause is known to create such information: Intelligence. Life was intelligently designed. Proteins prove it.
1:08

Proteins, the building blocks of all cells, prove Life is Intelligently designed. I'll prove it to you using an analogy. Look at the letters that make up these sentences. They are arranged into a specific pattern that gives the final arrangement functional significance. Letters don't convey any real meaning by themselves - it's not until they're arranged into a sentence that function arises. Proteins are very similar - they achieve functional significance in cells via specifically arranged amino acid sequences. Just as a single letter doesn't do anything by itself, a single amino acid is useless outside a full protein sequence. Evolution is supposed to build new proteins step by step, one amino acid at a time. But think about this: A Is that a meaningful sentence? A B How about that? A BALL BOUNCES. There we go. See, building the sentence one letter at a time provides no functional benefit - it's not until we have the full sequence that function emerges. It's the same with proteins. ...which means evolution can't build them one step at a time. They are all or nothing sequences that requires specific arrangements to be known and created immediately, or they don't function. Evolutionists will argue novel proteins can be evolved from already existing functional proteins. So they simply grant themselves the existence of proteins and claim random mutations can build new ones. Wrong again. There is only about 1 single functional protein fold - the shape an amino acid sequence makes when it becomes a functional protein - in about 10⁷⁷ possible amino acid sequences. That's a 10 with 77 zeroes. Those odds are overwhelmingly prohibitive. Tinkering with amino acid sequences destroys function after not too long, just like randomly changing letters in a word would destroy its meaning. Evolution cannot build novel proteins. No evidence exists showing how it can be done. Proteins exhibit what is called 'specified complexity.' That is, a complex arrangement that is enormously unlikely, unable to be explained by any repeatable pattern, and whose specifity grants function. Natural processes have never been observed to be able to create specified complexity. Only one cause is known to create such information: Intelligence. Life was intelligently designed. Proteins prove it.

Divinely Designed

11,564 次观看 • 1 个月前

This is how DNA turns raw data into functional proteins - the building blocks of all your cells. This system requires a minimum of 3 key players working together: DNA: the master blueprint with the instructions RNA Polymerase: reads the DNA and makes a temporary copy called mRNA which carries the instructions to the Ribosome for how to create the Protein Ribosome: the tiny factory that reads the mRNA and strings amino acids together in a specific sequence to create a protein Without all three molecules working together, Proteins cannot be created, cells don't function, and Life ends. Everything needs to fit together, precisely & perfectly, or it all falls apart. In other words: this system cannot evolve, one step at a time. DNA relies other machines made of proteins to create those very proteins - but those proteins can't be made without the information in the DNA. And on top of that, this whole system relies on OTHER systems! You need other things like ATP Synthase that makes energy to power everything, tRNA to carry the amino acids to the Ribosome, other helper proteins, processing enzymes, etc. It's an extremely complex, interdependent network of parts & systems that all rely on each other. The cell is an astounding level of complexity that surpasses anything in human engineering. It's obvious this is intelligently designed. To deny that is absurd.
2:15

This is how DNA turns raw data into functional proteins - the building blocks of all your cells. This system requires a minimum of 3 key players working together: DNA: the master blueprint with the instructions RNA Polymerase: reads the DNA and makes a temporary copy called mRNA which carries the instructions to the Ribosome for how to create the Protein Ribosome: the tiny factory that reads the mRNA and strings amino acids together in a specific sequence to create a protein Without all three molecules working together, Proteins cannot be created, cells don't function, and Life ends. Everything needs to fit together, precisely & perfectly, or it all falls apart. In other words: this system cannot evolve, one step at a time. DNA relies other machines made of proteins to create those very proteins - but those proteins can't be made without the information in the DNA. And on top of that, this whole system relies on OTHER systems! You need other things like ATP Synthase that makes energy to power everything, tRNA to carry the amino acids to the Ribosome, other helper proteins, processing enzymes, etc. It's an extremely complex, interdependent network of parts & systems that all rely on each other. The cell is an astounding level of complexity that surpasses anything in human engineering. It's obvious this is intelligently designed. To deny that is absurd.

Divinely Designed

22,903 次观看 • 8 个月前

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.
0:55

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 次观看 • 8 个月前

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 understood without motion, mechanism, and scale. Gō, Brooks & others showed that proteins possess characteristic collective motions - low-frequency normal modes that capture how whole molecules bend, breathe, and fluctuate. Frauenfelder then sharpened the picture further: proteins are not static objects occupying a single minimum, but dynamic ensembles traversing rugged energy landscapes. And yet the modern AI revolution in protein science has been, above all, a revolution in structure. In our new paper in Matter, Bo Ni and I ask a different question: not what structure will this sequence adopt? but what sequence will realize a prescribed pattern of motion? VibeGen inverts the conventional design paradigm. Rather than treating dynamics as a consequence to be analyzed after the fact, it makes dynamics the design objective from the outset. Using a language diffusion model with two cooperating agents - a designer that proposes sequences and a predictor that critiques them against the target motion profile - the system converges on de novo proteins with tailored vibrational behavior. One of the most intriguing results is a form of functional degeneracy - distinct sequences and distinct folds can satisfy the same target dynamical specification. For a given functional pattern of motion, evolution may have sampled only a small region of the physically realizable design space. The space of viable molecular mechanics may be far larger than the repertoire biology happened to discover. We have made "vibe" into a cultural metaphor - something intuitive, affective, subjective. But at the molecular scale, vibe is not metaphor: It is physics. For a protein, the vibe is the pattern of motion itself; the fluctuations, resonances, and collective displacements that determine what the molecule can do.
0:52

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 understood without motion, mechanism, and scale. Gō, Brooks & others showed that proteins possess characteristic collective motions - low-frequency normal modes that capture how whole molecules bend, breathe, and fluctuate. Frauenfelder then sharpened the picture further: proteins are not static objects occupying a single minimum, but dynamic ensembles traversing rugged energy landscapes. And yet the modern AI revolution in protein science has been, above all, a revolution in structure. In our new paper in Matter, Bo Ni and I ask a different question: not what structure will this sequence adopt? but what sequence will realize a prescribed pattern of motion? VibeGen inverts the conventional design paradigm. Rather than treating dynamics as a consequence to be analyzed after the fact, it makes dynamics the design objective from the outset. Using a language diffusion model with two cooperating agents - a designer that proposes sequences and a predictor that critiques them against the target motion profile - the system converges on de novo proteins with tailored vibrational behavior. One of the most intriguing results is a form of functional degeneracy - distinct sequences and distinct folds can satisfy the same target dynamical specification. For a given functional pattern of motion, evolution may have sampled only a small region of the physically realizable design space. The space of viable molecular mechanics may be far larger than the repertoire biology happened to discover. We have made "vibe" into a cultural metaphor - something intuitive, affective, subjective. But at the molecular scale, vibe is not metaphor: It is physics. For a protein, the vibe is the pattern of motion itself; the fluctuations, resonances, and collective displacements that determine what the molecule can do.

Markus J. Buehler

89,891 次观看 • 5 个月前

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.
0:59

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

15,956 次观看 • 8 个月前

This is concerning on so many levels: "No one knows what those proteins are doing" Professor Robert Clancy: "the Nobel Prize in 2023 was given to two people for putting pseudouridine in a messenger RNA [but the] pseudouridine [was producing]—instead of a spike protein—something completely strange and different" That Nobel Prize in 2023 meets a peer reviewed study from Cambridge, which might have outlined a mechanism behind why embalmers are seeing the "strange rubbery clots" in the deceased. AND, the Yale evidence of persistent spike production of 709 x days, however that's happening, gives a cautionary but plausible amyloidogenic mechanism for abnormal proteins to be produced both acutely and for extended periods. Professor Robert Clancy: "the Nobel Prize in 2023 was given to two people for putting pseudouridine in a messenger RNA, to make it work better" "Within three months, a group in Cambridge found that 20% of readouts, and about 10% of people, had strange proteins circulating in their bodies, some of which have the capacity to form amyloid, which can cause dementia [and] they found this within weeks and months of people being vaccinated" "They worked out that the mechanism was because the pseudouridine [was producing]—instead of a spike protein—something completely strange and different"
3:04

This is concerning on so many levels: "No one knows what those proteins are doing" Professor Robert Clancy: "the Nobel Prize in 2023 was given to two people for putting pseudouridine in a messenger RNA [but the] pseudouridine [was producing]—instead of a spike protein—something completely strange and different" That Nobel Prize in 2023 meets a peer reviewed study from Cambridge, which might have outlined a mechanism behind why embalmers are seeing the "strange rubbery clots" in the deceased. AND, the Yale evidence of persistent spike production of 709 x days, however that's happening, gives a cautionary but plausible amyloidogenic mechanism for abnormal proteins to be produced both acutely and for extended periods. Professor Robert Clancy: "the Nobel Prize in 2023 was given to two people for putting pseudouridine in a messenger RNA, to make it work better" "Within three months, a group in Cambridge found that 20% of readouts, and about 10% of people, had strange proteins circulating in their bodies, some of which have the capacity to form amyloid, which can cause dementia [and] they found this within weeks and months of people being vaccinated" "They worked out that the mechanism was because the pseudouridine [was producing]—instead of a spike protein—something completely strange and different"

Humanspective

202,591 次观看 • 1 年前

Friedberg: New study shows enzyme reverses skin age from 70+ years to 31 Chamath: That’s a $2T market. Did Scientists Just Discover How to Reverse Skin Aging!? “CML is kind of the predominant molecule that gets formed in this extracellular matrix that's driving aging, and nothing breaks it down. So these scientists set out to try and create an enzyme, an enzyme is a protein that breaks something down, that can break down CML. And so these guys kind of went out and they took the target, which is CML, and tried to figure out, ‘Okay, how do we actually degrade CML, clear that extracellular matrix, and reverse aging?’ They started to test it on the proteins that we would find in our body, casein, collagen, retinal proteins, which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degrade it away. And then they found several sites where they were able to degrade over 90%. And then they took actual human skin from elderly patients that had donated their skin, and they put this enzyme onto that skin, and they were able to eliminate 55% of the CML on the skin, basically reverse the skin's age down to the age of a 31-year-old, this is from greater than 70-year-old patients, just by putting this enzyme on the skin. And so it's kind of a groundbreaking demonstration of combination of AlphaFold, what's called directed evolution, where you change the order of the DNA that changes the structure of the protein to test different proteins, do high throughput screening, and ultimately make a novel protein that doesn't exist in nature today that can do something pretty profound for human health.” Chamath: “It will be a trillion-dollar market. If you can create a cream…” Friedberg: “I mean, dude, if you could put this enzyme literally on your skin and have it absorb in…” Chamath: “Game over. That alone is $2 trillion.”
1:42

Friedberg: New study shows enzyme reverses skin age from 70+ years to 31 Chamath: That’s a $2T market. Did Scientists Just Discover How to Reverse Skin Aging!? “CML is kind of the predominant molecule that gets formed in this extracellular matrix that's driving aging, and nothing breaks it down. So these scientists set out to try and create an enzyme, an enzyme is a protein that breaks something down, that can break down CML. And so these guys kind of went out and they took the target, which is CML, and tried to figure out, ‘Okay, how do we actually degrade CML, clear that extracellular matrix, and reverse aging?’ They started to test it on the proteins that we would find in our body, casein, collagen, retinal proteins, which are in your eye, hemoglobin, and they were able to get rid of 52 to 97% of the CML, just degrade it away. And then they found several sites where they were able to degrade over 90%. And then they took actual human skin from elderly patients that had donated their skin, and they put this enzyme onto that skin, and they were able to eliminate 55% of the CML on the skin, basically reverse the skin's age down to the age of a 31-year-old, this is from greater than 70-year-old patients, just by putting this enzyme on the skin. And so it's kind of a groundbreaking demonstration of combination of AlphaFold, what's called directed evolution, where you change the order of the DNA that changes the structure of the protein to test different proteins, do high throughput screening, and ultimately make a novel protein that doesn't exist in nature today that can do something pretty profound for human health.” Chamath: “It will be a trillion-dollar market. If you can create a cream…” Friedberg: “I mean, dude, if you could put this enzyme literally on your skin and have it absorb in…” Chamath: “Game over. That alone is $2 trillion.”

The All-In Podcast

2,983,249 次观看 • 1 个月前

Creator of C#, Anders Hejlsberg(Anders Hejlsberg), on the design goals that shaped the language and why standardisation was a goal from the beginning: “The overarching thing was this power and productivity of C++ with the ease of use of Visual Basic. We knew we wanted to build an object oriented language. We wanted managed code or byte code so we could target different runtime environments. We wanted garbage collection and exception handling, but also things like a unified object system where, and that's true in C#, anything can be assigned to an object. If it's a value type, we box it. And it's a self-describing object. So, reflection: you can ask an object, ‘what are you’? And you can get all of the facts about it at runtime, and you can dynamically manipulate it in ways that just don't exist in a lot of other environments. We wanted a language that made this new model of properties, methods and events first class because that was how components were built as opposed to just sort of functions and procedures and even objects. And we wanted to create a language that was standardised. We wanted to give this language to a standardisation committee and try to level the playing field there. And all of those things were sort of like what was rolled up in C#”
1:43

Creator of C#, Anders Hejlsberg(Anders Hejlsberg), on the design goals that shaped the language and why standardisation was a goal from the beginning: “The overarching thing was this power and productivity of C++ with the ease of use of Visual Basic. We knew we wanted to build an object oriented language. We wanted managed code or byte code so we could target different runtime environments. We wanted garbage collection and exception handling, but also things like a unified object system where, and that's true in C#, anything can be assigned to an object. If it's a value type, we box it. And it's a self-describing object. So, reflection: you can ask an object, ‘what are you’? And you can get all of the facts about it at runtime, and you can dynamically manipulate it in ways that just don't exist in a lot of other environments. We wanted a language that made this new model of properties, methods and events first class because that was how components were built as opposed to just sort of functions and procedures and even objects. And we wanted to create a language that was standardised. We wanted to give this language to a standardisation committee and try to level the playing field there. And all of those things were sort of like what was rolled up in C#”

The Pragmatic Engineer

18,332 次观看 • 3 个月前

For decades, biologists argued that birds migrate using magnetic fields, and that cryptochrome proteins in their eyes help them figure out where to fly. But the evidence for this has always been flimsy. In 1972, Wolfgang and Roswitha Wiltschko captured migratory European robins, put them in cages, covered the cages with a blanket, and wrapped electric coils around them. Once the birds lost their view of the sky, they still tried to move, or "hop," in the direction of their normal migration route. But when the Wiltschkos flipped the magnetic field around, the robins started hopping in random directions. They took this as evidence that, somehow, birds migrate using a magnetic sense. (Not bad!) In 2000, three theoretical biophysicists in Illinois, Ritz, Adem, and Schulten, proposed a mechanism for that magnetic sense. They argued that when blue light hits a receptor in the eye, it might create something called a "radical pair," locking two electrons into a spin state that a magnetic field could then nudge. They suggested that cryptochromes, light-sensitive proteins in the retina, might be responsible. (Speculative!) And then, in 2021, researchers apparently confirmed this! They took cryptochrome proteins from a type of migratory robin and put them in a test tube. They shone blue light at the proteins and found that this light induced them to form that transient "radical pair" state. And finally, they showed that magnetic fields could change this photochemistry where, in the presence of a magnetic field, the proteins formed fewer of these radical pairs, because the field forced a larger fraction of the excited molecules to ‘collapse’ back to their resting state. The experiment they used to measure this, though, has almost nothing to do with biology. You literally isolate the proteins, bombard them with a blue laser and, after each pulse, measure how much light the proteins absorb. For the robin cryptochrome protein, adding a magnetic field changed the absorbance *slightly.* But here’s the caveat: All of this was done in vitro, in a test tube, in a water-based buffer (rather than a cell). And, even worse, the experiment was done at 5 degrees Celsius (waaaay colder than the bird’s normal temperature) and at a low pH. And even after all this tinkering, they still *barely* saw a magnetic response! The news media didn't report many of these caveats. I randomly pulled one story from Science News and another from the University of Oxford, and neither even mentioned that the researchers ran the experiment at low temperature. The Oxford writeup actually hyped the result up more than the paper itself; that author wrote: “…the authors think the proteins involved could be significantly more sensitive in their native environment. In cells in the retina, the proteins are probably fixed and aligned, increasing their sensitivity to the direction of the magnetic field. Moreover, they are also likely to be associated with other proteins that could amplify the sensory signals." (Wow!) When Andrew York and Maria Ingaramo, two scientist working at Calico, heard about these results, they grew skeptical and decided to search for magnetically-responsive proteins — that actually work under physiological conditions — on their own. And that search, in turn, gave rise to Nonfiction Laboratories, a company that not only has created such proteins, but is now trying to commercialize them to make magnetically controlled cancer therapies that are only active near a tumor. The clip below is from my podcast.
2:53

For decades, biologists argued that birds migrate using magnetic fields, and that cryptochrome proteins in their eyes help them figure out where to fly. But the evidence for this has always been flimsy. In 1972, Wolfgang and Roswitha Wiltschko captured migratory European robins, put them in cages, covered the cages with a blanket, and wrapped electric coils around them. Once the birds lost their view of the sky, they still tried to move, or "hop," in the direction of their normal migration route. But when the Wiltschkos flipped the magnetic field around, the robins started hopping in random directions. They took this as evidence that, somehow, birds migrate using a magnetic sense. (Not bad!) In 2000, three theoretical biophysicists in Illinois, Ritz, Adem, and Schulten, proposed a mechanism for that magnetic sense. They argued that when blue light hits a receptor in the eye, it might create something called a "radical pair," locking two electrons into a spin state that a magnetic field could then nudge. They suggested that cryptochromes, light-sensitive proteins in the retina, might be responsible. (Speculative!) And then, in 2021, researchers apparently confirmed this! They took cryptochrome proteins from a type of migratory robin and put them in a test tube. They shone blue light at the proteins and found that this light induced them to form that transient "radical pair" state. And finally, they showed that magnetic fields could change this photochemistry where, in the presence of a magnetic field, the proteins formed fewer of these radical pairs, because the field forced a larger fraction of the excited molecules to ‘collapse’ back to their resting state. The experiment they used to measure this, though, has almost nothing to do with biology. You literally isolate the proteins, bombard them with a blue laser and, after each pulse, measure how much light the proteins absorb. For the robin cryptochrome protein, adding a magnetic field changed the absorbance *slightly.* But here’s the caveat: All of this was done in vitro, in a test tube, in a water-based buffer (rather than a cell). And, even worse, the experiment was done at 5 degrees Celsius (waaaay colder than the bird’s normal temperature) and at a low pH. And even after all this tinkering, they still *barely* saw a magnetic response! The news media didn't report many of these caveats. I randomly pulled one story from Science News and another from the University of Oxford, and neither even mentioned that the researchers ran the experiment at low temperature. The Oxford writeup actually hyped the result up more than the paper itself; that author wrote: “…the authors think the proteins involved could be significantly more sensitive in their native environment. In cells in the retina, the proteins are probably fixed and aligned, increasing their sensitivity to the direction of the magnetic field. Moreover, they are also likely to be associated with other proteins that could amplify the sensory signals." (Wow!) When Andrew York and Maria Ingaramo, two scientist working at Calico, heard about these results, they grew skeptical and decided to search for magnetically-responsive proteins — that actually work under physiological conditions — on their own. And that search, in turn, gave rise to Nonfiction Laboratories, a company that not only has created such proteins, but is now trying to commercialize them to make magnetically controlled cancer therapies that are only active near a tumor. The clip below is from my podcast.

Niko McCarty.

21,714 次观看 • 23 天前