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[return to "AlphaFold reveals the structure of the protein universe"]
1. crispy+Ww[view] [source] 2022-07-28 14:36:46
>>MindGo+(OP)
I got a 5th grader question about how proteins are used/represented graphically that I've never been able to find a satisfying answer for.

Basically, you see these 3D representations of specific proteins as a crumple of ribbons-- literally like someone ran multi-colored ribbons though scissors to make curls and dumped it on the floor (like a grade school craft project).

So... I understand that proteins are huge organic molecules composed of thousands of atoms, right? Their special capabilities arise from their structure/shape. So basically the molecule contorts itself to a low energy state which could be very complex but which enables it to "bind?" to other molecules expressly because of this special shape and do the special things that proteins do-- that form the basis of living things. Hence the efforts, like Alphafold, to compute what these shapes are for any given protein molecule.

But what does one "do" with such 3D shapes?

They seem intractably complex. Are people just browsing these shapes and seeing patterns in them? What do the "ribbons" signify? Are they just some specific arrangement of C,H,O? Why are some ribbons different colors? Why are there also thread-like things instead of all ribbons?

Also, is that what proteins would really look like if you could see at sub-optical wavelength resolutions? Are they really like that? I recall from school the equipartition theorem-- 1/2 KT of kinetic energy for each degree of freedom. These things obviously have many degrees of freedom. So wouldn't they be "thrashing around" like rag doll in a blender at room temperature? It seems strange to me that something like that could be so central to life, but it is.

Just trying to get myself a cartoonish mental model of how these shapes are used! Anyone?

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2. dekhn+jy[view] [source] 2022-07-28 14:41:27
>>crispy+Ww
The ribbons and helices you see in those pictures are abstract representations of the underlying positions of specific arrangements of carbon atoms along the backbone.

There are tools such as DSSP https://en.wikipedia.org/wiki/DSSP_(hydrogen_bond_estimation... which will take out the 3d structure determined by crystallography and spit out hte ribbons and helices- for example, for helices, you can see a specific arrangement of carbons along the protein's backbone in 3d space (each carbon interacts with a carbon 4 amino acids down the chain).

Protein motion at room temperature varies depending on the protein- some proteins are rocks that stay pretty much in the same single conformation forever once they fold, while others do thrash around wildly and others undergo complex, whole-structure rearrangements that almost seem magical if you try to think about them using normal physics/mechanical rules.

Having a magical machine that could output the full manifold of a protein during the folding process at subatomic resolution would be really nice! but there would be a lot of data to process.

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3. crispy+ez[view] [source] 2022-07-28 14:44:58
>>dekhn+jy
Thanks, awesome! So what do molecular biologists do with these 3D representations once they have them? Do they literally just see how they fit to other proteins?
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4. buntsa+KC[view] [source] 2022-07-28 15:00:01
>>crispy+ez
Often the ribbons (alpha-helices and beta=sheets) form "protein domains". Canonically, these are stable, folded structures with conserved shapes and functions that serve as the building blocks of proteins, like lego pieces. These protein domains can be assembled in different ways to form proteins of different function. Different protein domains that have the same evolutionary origin have conserved structure even when the underlying amino acid sequence, or DNA sequence has changed beyond recognition over millions of years of evolution. In other words, molecular biologists use structure as a proxy for function. Looking at how the same protein domains works in different proteins in different species can give us clues as to how a protein might work in human biology or disease.
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