6 ms·

You are basically made of proteins, which are basically folded sequences of amino acids, proteins are molecular machines that are the fundamental building block

You are basically made of proteins, which are basically folded sequences of amino acids, proteins are molecular machines that are the fundamental building block of animals, plants, bacteria, fungi, viruses etc. So yeah the applications are enormous, from medicine to better industrial chemical processes, from warfare to food manufacturing.

jebarker 4y ago
> proteins are molecular machines Does that imply proteins have some dynamics that need to be predicted too? I remember seeing animations of molecular machines that appeared to be "walking" inside the body - are those proteins or more complex structures?
- gilleain 4y ago
  Yes, very much so. Even for proteins that seems like they are just scaffolding for a catalytic centre can have important dynamics. A classic example is haemoglobin, that 'just' binds to oxygen at the iron in the middle of the haem. Other binding sites remote from the oxygen binding one can bind to other molecules - notably carbon dioxide. The 'Bohr effect' mechanism is outlined here : https://en.wikipedia.org/wiki/Bohr_effect#Allosteric_interactions https://en.wikipedia.org/wiki/Bohr_effect#Allosteric_interac... Even at the lowest level, there is some evidence that ligand binding can affect the structure of the backbone of the protein. For example, peptide plane flipping https://en.wikipedia.org/wiki/Peptide_plane_flipping https://en.wikipedia.org/wiki/Peptide_plane_flipping although I'm not sure where the research is on this nowadays.
  - jebarker 4y ago
    Fascinating. I'm a mathematician turned AI researcher by day. The more I learn about biology the more I feel that our human engineering (hard and soft) is trivially simple compared to what evolution has already created and left for us to study.
    - gilleain 4y ago
      Heh, I'm somewhat the opposite, as I went from a degree in biochemistry into bioinformatics (protein folds and structure) and have an amateur interest in maths. I often recommend the book 'Cats' Paws and Catapults' by Steven Vogel, which discusses the differences between human and biological engineering. There are very different constraints, as well as the more obvious difference between intelligently directed design (by humans) and evolutionary design. It's not totally true that our engineering is simpler than biological systems. After all, we can now manipulate matter down to the atomic level. There have been attempts to move towards self-assembling systems, or even self-repairing ones. Not quite on the same scale or sophistication as biological systems, of course. Is a modern computer chip more complex than a virus? Is a large connected system of computers more complex than a mycelial network? Are there more parts connected in more ways in a nuclear power station as there are in a simple bacterial cell? I think it is definitely worth considering the similarities and differences.
      - jebarker 4y ago
        Definitely interesting comparisons. I think my sense that biology is more complex than human engineering is that our engineering seems much more homogeneous. Computer chips are certainly very dense but the individual number of different component types are very small. Biology on the other hand seems to have a huge number of fundamental building blocks, e.g. proteins, with different behaviors. I suppose that maybe that's the wrong comparison though and software is where our engineering diversity is present. It may well just be the case that my lack of familiarity with biology makes it seem more complex to me.
        ncmncm 4y ago
        One person can, at least in principle, understand every last thing in a nuclear reactor. A few elements have roles at different levels of abstraction. And of course they have computers in them that invariably do stuff radically simpler than they could be doing. But nobody will ever understand everything about a natural cell. Levels are an ad hoc phenomenon adhered to in varying degrees in certain places to contain variation. But few elements have only one role at one identifiable level, and you can never be sure one doesn't have another. And huge amounts of apparatus might radically change behavior in a subtly different environment.
- fabiospampinato 4y ago
  Yes proteins can be dynamic, and multiple proteins can come together to form bigger structures (like a cell's membrane for example), and they can very much interact with other proteins and molecules in complex ways. I think AlphaFold gives us more of a static picture that doesn't tell us much about how the protein will interact with the world. Predicting these dynamic aspects, protein-to-protein interactions, and ultimately an entire cell, is probably what they'll like to do next. I don't know if the walking buddy is a single protein, it may be a handful of different ones joined together.
- Alop3x 4y ago
  Reference: https://en.wikipedia.org/wiki/Kinesin https://en.wikipedia.org/wiki/Kinesin , https://en.wikipedia.org/wiki/Dynein https://en.wikipedia.org/wiki/Dynein , https://en.wikipedia.org/wiki/Myosin https://en.wikipedia.org/wiki/Myosin They are called motor proteins because they convert chemical energy into kinetic energy. In the case of kinesin, it forms a dimer (two copies of itself bind together to form the two "legs") and also binds to light chains (accessory proteins that modulate its behavior) so that it can walk along filaments and drag cargo around your cells. They are both proteins and more complex structures because multiple proteins are interacting, as well as binding small molecules and catalyzing them into chemical products, all to produce the motion.

jebarker 4y ago

> proteins are molecular machines Does that imply proteins have some dynamics that need to be predicted too? I remember seeing animations of molecular machines that appeared to be "walking" inside the body - are those proteins or more complex structures?

gilleain 4y ago
Yes, very much so. Even for proteins that seems like they are just scaffolding for a catalytic centre can have important dynamics. A classic example is haemoglobin, that 'just' binds to oxygen at the iron in the middle of the haem. Other binding sites remote from the oxygen binding one can bind to other molecules - notably carbon dioxide. The 'Bohr effect' mechanism is outlined here : https://en.wikipedia.org/wiki/Bohr_effect#Allosteric_interactions https://en.wikipedia.org/wiki/Bohr_effect#Allosteric_interac... Even at the lowest level, there is some evidence that ligand binding can affect the structure of the backbone of the protein. For example, peptide plane flipping https://en.wikipedia.org/wiki/Peptide_plane_flipping https://en.wikipedia.org/wiki/Peptide_plane_flipping although I'm not sure where the research is on this nowadays.
- jebarker 4y ago
  Fascinating. I'm a mathematician turned AI researcher by day. The more I learn about biology the more I feel that our human engineering (hard and soft) is trivially simple compared to what evolution has already created and left for us to study.
  - gilleain 4y ago
    Heh, I'm somewhat the opposite, as I went from a degree in biochemistry into bioinformatics (protein folds and structure) and have an amateur interest in maths. I often recommend the book 'Cats' Paws and Catapults' by Steven Vogel, which discusses the differences between human and biological engineering. There are very different constraints, as well as the more obvious difference between intelligently directed design (by humans) and evolutionary design. It's not totally true that our engineering is simpler than biological systems. After all, we can now manipulate matter down to the atomic level. There have been attempts to move towards self-assembling systems, or even self-repairing ones. Not quite on the same scale or sophistication as biological systems, of course. Is a modern computer chip more complex than a virus? Is a large connected system of computers more complex than a mycelial network? Are there more parts connected in more ways in a nuclear power station as there are in a simple bacterial cell? I think it is definitely worth considering the similarities and differences.
    - jebarker 4y ago
      Definitely interesting comparisons. I think my sense that biology is more complex than human engineering is that our engineering seems much more homogeneous. Computer chips are certainly very dense but the individual number of different component types are very small. Biology on the other hand seems to have a huge number of fundamental building blocks, e.g. proteins, with different behaviors. I suppose that maybe that's the wrong comparison though and software is where our engineering diversity is present. It may well just be the case that my lack of familiarity with biology makes it seem more complex to me.
      - ncmncm 4y ago
        One person can, at least in principle, understand every last thing in a nuclear reactor. A few elements have roles at different levels of abstraction. And of course they have computers in them that invariably do stuff radically simpler than they could be doing. But nobody will ever understand everything about a natural cell. Levels are an ad hoc phenomenon adhered to in varying degrees in certain places to contain variation. But few elements have only one role at one identifiable level, and you can never be sure one doesn't have another. And huge amounts of apparatus might radically change behavior in a subtly different environment.
fabiospampinato 4y ago
Yes proteins can be dynamic, and multiple proteins can come together to form bigger structures (like a cell's membrane for example), and they can very much interact with other proteins and molecules in complex ways. I think AlphaFold gives us more of a static picture that doesn't tell us much about how the protein will interact with the world. Predicting these dynamic aspects, protein-to-protein interactions, and ultimately an entire cell, is probably what they'll like to do next. I don't know if the walking buddy is a single protein, it may be a handful of different ones joined together.
Alop3x 4y ago
Reference: https://en.wikipedia.org/wiki/Kinesin https://en.wikipedia.org/wiki/Kinesin , https://en.wikipedia.org/wiki/Dynein https://en.wikipedia.org/wiki/Dynein , https://en.wikipedia.org/wiki/Myosin https://en.wikipedia.org/wiki/Myosin They are called motor proteins because they convert chemical energy into kinetic energy. In the case of kinesin, it forms a dimer (two copies of itself bind together to form the two "legs") and also binds to light chains (accessory proteins that modulate its behavior) so that it can walk along filaments and drag cargo around your cells. They are both proteins and more complex structures because multiple proteins are interacting, as well as binding small molecules and catalyzing them into chemical products, all to produce the motion.