The Unreasonable Redundancy of Nature's Protein Folds
research.ligo.bio
The Unreasonable Redundancy of Nature's Protein Folds
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Re: The Unreasonable Redundancy of Nature's Protein Folds
#2This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism.
Re: The Unreasonable Redundancy of Nature's Protein Folds
#3cool post! it's funny how many things in this world are naturally graphs. i think it's neat how, especially in biology, a lot of high-dimensional objects, like protien sequences, converge onto lower-dimensional representations, like protein structures.
i did neuroscience for grad school, and i was always amazed by how often complex neural activity could be well represented by lower dimensional representations--clean manifolds, attractor dynamics, etc. i think, in general, biology (evolution) doesn't penalize against redundancy too hard (hence things like genetic drift, neutral theory of evolution, etc.).
anyway, super cool stuff. agree with you that probs more useful to explore the search space via 'less natural' structures, given how forgiving evolution is to redundancy. probs where the most information can be found
Re: The Unreasonable Redundancy of Nature's Protein Folds
#4This crashed my browser. Use reader mode.
Re: The Unreasonable Redundancy of Nature's Protein Folds
#5This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism. https://www.science.org/doi/10.1126/science.adq4946
What plagiarism even means in context of proteins? That one protein steals a fold of another protein without giving proper credit to it?
Re: The Unreasonable Redundancy of Nature's Protein Folds
#6No real clue what this stuff is about, way over my head, but kudos on an article where it's all there on the page instead of needing scripts to pull text and images from different places!
Re: The Unreasonable Redundancy of Nature's Protein Folds
#7This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism. https://www.science.org/doi/10.1126/science.adq4946
They found "several thousand" novel folds? I had remembered that there were around 1000:
https://pmc.ncbi.nlm.nih.gov/articles/PMC7072414/
Oh ok, I misremembered:
"This review has focused only on small fragments of fold space with examples given for folds generated from a single secondary structure string consisting of around ten SSEs. Even in this small corner, the number of possible folds, under the current constraints, is of the order of 1000"
Re: The Unreasonable Redundancy of Nature's Protein Folds
#8This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism. https://www.science.org/doi/10.1126/science.adq4946
What plagiarism even means in context of proteins? That one protein steals a fold of another protein without giving proper credit to it?
I understood it as metaphor - just that evolutionarily distant sequences can adopt the same (or very similar) folds because there are only a limited number of stable, accessible folds that are possible.
Re: The Unreasonable Redundancy of Nature's Protein Folds
#9This approach is pretty much like the TED approach from a few years back. As far as I remember there wasn’t a ridiculous amount of fold diversity there either. It turns out evolution isn’t averse to a bit of liberal protein plagiarism. https://www.science.org/doi/10.1126/science.adq4946
They found "several thousand" novel folds? I had remembered that there were around 1000: https://pmc.ncbi.nlm.nih.gov/articles/PMC7072414/ Oh ok, I misremembered: "This review has focused only on small fragments of fold space with examples given for folds generated from a single secondary structure string consisting of around ten SSEs. Even in this small corner, the number of possible folds, under the current constra…
I think there was a Twitter/Bluesky thread on the results from adding all the predicted folds from metagenomics too, and not ending up with many new clusters. If this continues to hold true as we keep looking at stuff, I will be relieved that at least natural protein folds and domains has a limited (tractable) solution space. All we need to do now is annotate the variation of these couple of thousands of fold variants. Challenging, but at least a bounded problem.
Re: The Unreasonable Redundancy of Nature's Protein Folds
#10Earlier quoted context omitted.
What plagiarism even means in context of proteins? That one protein steals a fold of another protein without giving proper credit to it?
I understood it as metaphor - just that evolutionarily distant sequences can adopt the same (or very similar) folds because there are only a limited number of stable, accessible folds that are possible.
Yes, that is exactly what I meant! Here’s an experiment to try: Frances Arnold got a nobel prize for work related to directed evolution. However, we know evolution is limited by the tools available to it as you mention. If we add random chaperones and co-factors to bacteria that we know other organisms use, can we push evolution outside of the known fold space? Is the limited fold space an absolute limit or the “accessible” limit?