31–40 of 63 posts
Can we please retire the headline trend of "The Unreasonable ___ of ____ "
It seems to have originated with Eugene Wigner's 1960 "The Unreasonable Effectiveness of Mathematics in the Natural Sciences".
This is just repeating the fact that the proteins life actually uses are a very small part of the total possible ones. First, there's no real length limit, but all life's proteins are limited to a few thousand amino acids. Most barely get past hundred. (note: there are bigger proteins, including ones so big you can see them with the naked eye (e.g. a hair) but they consists of multiple repeats of the same small build…
I like how you say evolution is able to think when in reality it's just a mysterious function of variation, selection, and time.
Can we please retire the headline trend of "The Unreasonable ___ of ____ "
None of this seems particularly surprising to someone who was an undergraduate level of biochemistry knowledge. Thirty years ago the professor in my Proteins class made a few relevant important points in his lectures: 1) Only handful of amino acids in a enzyme structures were highly conserved. (Out of hundreds, generally less than ten.) 2) Those were generally in the reaction center. 3) Almost all single sequence rep…
- that structure is as/more important than sequence ?
- that "reaction centers" are what matter, and the rest is just "protection" ?
What do you mean by "reaction center" - surely not physically central within the folded structure (isn't it the surface shape that determines reactivity) ?
None of this seems particularly surprising to someone who was an undergraduate level of biochemistry knowledge. Thirty years ago the professor in my Proteins class made a few relevant important points in his lectures: 1) Only handful of amino acids in a enzyme structures were highly conserved. (Out of hundreds, generally less than ten.) 2) Those were generally in the reaction center. 3) Almost all single sequence rep…
So what are the lessons here? - that structure is as/more important than sequence ? - that "reaction centers" are what matter, and the rest is just "protection" ? What do you mean by "reaction center" - surely not physically central within the folded structure (isn't it the surface shape that determines reactivity) ?
Structure is determined by sequence, so they are equally important. Structure is more conserved than sequence, mainly due to the physicochemical constraints that govern protein folding.
> that "reaction centers" are what matter, and the rest is just "protection"?
Sometimes not even protection. Many enzymes can have plenty of its sequence/structure removed and still be functional. Natural proteins carry lots of evolutionary cruft.
> What do you mean by "reaction center" - surely not physically central within the folded structure
I think they borrowed the term from photosystems/photosynthesis. But, to be more precise, what they actually meant is the active site of an enzyme; the location where the catalyzed reaction takes place.
> (isn't it the surface shape that determines reactivity) ?
Shape is not enough, the chemical nature of the amino acid residues involved is also important. A single mutation in a key catalytic residue will shut down the enzyme even if the shape stays the same.
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This reminds me of structural studies in proteins encoded by de novo genes in eukaryotes. They are usually either intrinsically disordered or adopt a molten-globule-like state.
Yes, I was watching a video about that the other day - the 'dark proteome' or the 'ghost proteome' or similar.
Note: the rest of the protein being so massive has the huge problem that it results in the chlorophyll protein being toxic (even to plants). Several angles of the protein reflect the light ... away from the energy collector (it has sections that are like putting a mirror above a solar panel). Also: it's extremely INefficient. Inefficiency gets solved "the DNA way" (or should I say the Zapp Brannigan way): it's efficiency sucks, but if I just use very extremely large armies of chloroplasts I can compensate for the inefficiency by stacking them ... This sounds totally insane but yes, it works. Oh and the exact right amount of inefficiency can warm op the plant, protecting it (a little bit) from ice ages.
Now I have my suspicions on why chlorophyll + chloroplasts won (it's not actually the only photosynthesis protein or system): it's because by tuning a few amino acids you can change the depth of the ion trap, and so switch to different metals to capture, changing the color (which plants do, even just to have a particular color). It's pretty easy to accidentally adapt to either different metals or different solar frequencies (ie. using natural selection). Plus there was no need to design chlorophyll: plants "stole" the design from bacteria. So it was incredibly cheap in terms of how much computation (ie. generations of plants) had to die to make it. Of course, for the place it was stolen from the length of the protein was a very important factor so the biggest of chlorophyll's advantages (1 big protein, 10 functions that would have required 5x more space in DNA with small proteins) don't actually matter to plants. So why did it win? It was on sale!
So it works. But there has got to be a simpler/better/non-toxic way to create an ion trap using proteins and make plants work better ... I get that part of the problem is that I'm an engineer, a scientist. If one needs a design to catch energy and warm up a plant, I'd expect to create one thing for catching energy, and one plant warmer, both efficient. So there's an expectation problem. But a single mechanism to mostly randomly warm plants and catch energy at the cost of absurd inefficiency (both in warming and in energy production) ... is just not a sane way to go about this problem.
Earlier quoted context omitted.
Yes, I was watching a video about that the other day - the 'dark proteome' or the 'ghost proteome' or similar.
But if you look at actual proteins where the function is pretty direct, you see ... a total mess. For example, the actual light catcher for photosynthesis, chlorophyll, you see rather suboptimal architecture. There is a central magnesium ion, and the entire rest of the protein is just there to keep it where it is. The only function, in other words, is to create an ion trap a a specific voltage. That's what that massi…
> So it works. But there has got to be a simpler/better/non-toxic way to create an ion trap using proteins and make plants work better ...
I remember reading about designed minimal photosystem-like systems. I cannot find the actual paper now, though.
This 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
> Natural selection has no analogy with any aspect of human behavior, However, if one wanted to play with a comparision, one would have to say natural selection does not work as an engineer works. It works like a tinkerer - a tinkerer who does not know exactly what he is going to produce but uses whatever he finds around him whether it be pieces of string, fragments or wood, or old cardboards; in short it works like…
Earlier quoted context omitted.
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 “acce…
I see. I meant 'energetically accessible', but you mean more like 'affordably accessible' (in the sense that the molecular toolkit of a cell is what can 'afford' certain structures, due to chaperones available and so on). Who knows what might be possible if you designed a cell from scratch - perhaps you could rework all the machinery to access other parts of fold space. After all, there are some weird and wonderful m…
Can we please retire the headline trend of "The Unreasonable ___ of ____ "
But then, this thead is all about proteins incorporating structural cliches, isn't it?