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Could someone confirm what we’re looking at in that picture please? In that spider web of blue points joined by blue line segments: Those tiny blue points are a

Could someone confirm what we’re looking at in that picture please? In that spider web of blue points joined by blue line segments: Those tiny blue points are atoms? The blue line segments are covalent bonds? And what’s the difference between the blue and purple areas? If those line segments are probability distributions of shared electrons, that means our high school mental model of a covalent bond (drawing a line between two atoms) is not too bad.

natechols 6y ago
The line segments define surfaces around the regions of highest electron density. This is how X-ray crystallographers traditionally viewed electron density, probably because that simple mesh was the best that early computer graphics systems could handle. In this particular image they've shown nested surfaces - my guess would be at 1 (purple), 2, and 3 standard deviations above the mean, or something like that. Again, not atoms, just electron clouds, but obviously the regions around the atoms have the most electrons.
- mysterypie 6y ago
  So it’s not like what I thought at all. If I understand you correctly, then each one of those bright blue balls is a cloud of electrons at the center of which is a nucleus (but we don’t see the nucleus itself). The tiny blue lines and vertices are just computer generated imagery to define the “surface” of an atom. Those hexagons with six blue balls joined by purple mesh are benzene rings? So each purple area defines a cloud of shared electrons in a benzene ring?
  - natechols 6y ago
    Mostly correct, except it's only indirectly the surface of the "atom" - because of the way covalent bonding works, there's continuous electron density between atoms too. It's just that the region around the nucleus is the most electron-dense. And yes, those look like phenylalanine or tyrosine (amino acid) sidechains to me, both of which have a benzene ring at the core. (For the record, there is also something called neutron crystallography, which works like X-ray crystallography except it's the nuclei that diffract, not the electron clouds - which allows you to visualize hydrogen atoms more directly, and even resolve the difference between hydrogen and deuterium. But it's another speciality technique, in part because neutron sources are so much weaker.) EDIT: since I actually did some work on visualizing electron density maps on the web, here's an interactive view of an older X-ray structure (from 2003, at only 3Å resolution) that shows how a protein molecule fits into the density: http://natechols.github.io/xtal.js/map_viewer.html http://natechols.github.io/xtal.js/map_viewer.html (click and hold the middle mouse button to pan through the molecule)
  - mncharity 6y ago
    > computer generated imagery to define the “surface” of an atom The grids are isosurfaces of electron density. Analogous to isolines on a map illustrating mountain terrain height. Atoms are sticky little fuzzy balls. The fuzz, electron density, falls off exponentially. They don't have an "edge" in a non-fuzzy-object sense. Analogous to a stereotype volcano having an arbitrary perimeter. Where would I place it? Where you need climbing gear? Where biking up gets hard? In the foothills? Somewhere on the sloped plain? You place the perimeter wherever is convenient for what you're trying to use it for. People are usually interested in the densities between sticking atoms, which are several orders of magnitude down from peak density. Analogous to drawing an isoline at "the towering volcano is here high enough to start stubbing your toe on it". The picture draws isosurfaces of electron density at something like "around here one atom would 'bump' another, and you can see bonds" and at "I wrap a single atom only, but still have an interesting shape". To show the various features of interest, one draws multiple isosurfaces. As with a terrain map. But an exponential electron density scale is harder to represent than linear height scale. And it's hard to clearly draw more than a couple of nested 3D isosurfaces. So instead of placing many iso's at linear steps, here there are just a couple, more like an order of magnitude apart.
    - natechols 6y ago
      The terrain analogy is great - this is how the first structural biologists had to view electron density: https://image.slideserve.com/105608/electron-density-maps-of-proteins-sperm-whale-myoglobin-2-4-angstrom-resolution-l.jpg https://image.slideserve.com/105608/electron-density-maps-of... I think this is a stack of 2d "slices" through the density, printed on transparencies. But I've also seen 2d representations of charge density (some of which is just theoretical studies) that are even more similar to a terrain map.
      - mncharity 6y ago
        Neat. I've been exploring visual representations of electron density, optimized for educational use with XR. Intending to illustrate that science education content could be made transformatively less wretched. Isosurfaces and nonlinear color gradients are educationally problematic. And fuzz gradients are hard to visually stereo fuse. And on near-term AR displays, black is transparent, and background environment colors can't be manipulated, which limits the space of attainable colorizations. My current thought is to approach it as a volumetric light source. Composed of several linear scales, each a different color, with density as transparency. And respecting their true density when combined, so higher density scales "shine through" lower. We'll see. Maybe overlay random sample "sparkles" to maybe improve sense of spatial extent. I've not seen much similar work. If you know of any, I'd love to hear of it. Also, it seems there was a push some years back to emphasize electron density when teaching intro chemistry. A push that doesn't seem to have gelled. I've guesses, but I'd value thoughts on why.
  - voxelghost 6y ago
    The nucleus is on the scale of 10e-5 (1/100,000) to the size of the whole atom (cloud).
    - Koshkin 6y ago
      Yet, the maximum density of the electron cloud (at least in the case of s-orbitals) is right inside it. (Talk about the "size of the whole atom"!)
pas 6y ago
Very good question. It'd be great to understand how this whole imaging process works. I have no idea, but it seems it involves many photos and rotation, and then DSP. So it's like CT for proteins .. maybe. It's like the x-ray crystallography but instead of repeating the x-ray many times on many-many samples. (edited) https://kpwulab.wordpress.com/2018/12/13/a-1-96-a-cryoem-map-of-mouse-apo-ferritin-determined-by-kps-group/ https://kpwulab.wordpress.com/2018/12/13/a-1-96-a-cryoem-map... https://cryoem.med.ubc.ca/image-gallery/ https://cryoem.med.ubc.ca/image-gallery/ https://cemas.osu.edu/news/2019/03/exciting-cryo-em-updates https://cemas.osu.edu/news/2019/03/exciting-cryo-em-updates https://elifesciences.org/articles/25648.pdf https://elifesciences.org/articles/25648.pdf
- natechols 6y ago
  Not many samples, many copies of the protein in what is often a single crystal (although if it's easily damaged, you might to use multiple crystals and combine the data post-processing). EM is actually very destructive, so they have to take thousands of micrographs of different individual molecules, and average them together.
  - pas 6y ago
    Oh, okay, thanks! I've edited my comment to be hopefully less wrong. So it's like the x-ray version, just a different approach / energy scale? Or is that comparison ... doesn't make sense?
    - natechols 6y ago
      Both techniques give you the average electron density over thousands to billions of molecules. The difference is in what kind of data you actually collect, and how you process and combine the data to get that averaged map: - In X-ray crystallography, you're collecting the amplitudes of the Fourier transform of the electron density in the repeating unit of the crystal. The fact that it's a well-ordered (usually) crystal effectively "amplifies" the FT, and you get a series of images like this (from one orientation of the crystal): https://cdn.britannica.com/02/147302-050-3F732246/X-ray-diffraction-pattern-enzyme.jpg https://cdn.britannica.com/02/147302-050-3F732246/X-ray-diff... - In EM, you're collecting direct images of particles randomly distributed on a grid, but they're 2D and individually very noisy, like this: https://www.pnas.org/content/pnas/110/45/18037/F3.large.jpg?width=800&height=600&carousel=1 https://www.pnas.org/content/pnas/110/45/18037/F3.large.jpg?... In either case, there's a lot of complex math that goes into reconstructing the electron density - but the end result, the electron density map, is very similar (aside from the absence of crystal packing interactions in the EM map).

natechols 6y ago

The line segments define surfaces around the regions of highest electron density. This is how X-ray crystallographers traditionally viewed electron density, probably because that simple mesh was the best that early computer graphics systems could handle. In this particular image they've shown nested surfaces - my guess would be at 1 (purple), 2, and 3 standard deviations above the mean, or something like that. Again, not atoms, just electron clouds, but obviously the regions around the atoms have the most electrons.

mysterypie 6y ago
So it’s not like what I thought at all. If I understand you correctly, then each one of those bright blue balls is a cloud of electrons at the center of which is a nucleus (but we don’t see the nucleus itself). The tiny blue lines and vertices are just computer generated imagery to define the “surface” of an atom. Those hexagons with six blue balls joined by purple mesh are benzene rings? So each purple area defines a cloud of shared electrons in a benzene ring?
- natechols 6y ago
  Mostly correct, except it's only indirectly the surface of the "atom" - because of the way covalent bonding works, there's continuous electron density between atoms too. It's just that the region around the nucleus is the most electron-dense. And yes, those look like phenylalanine or tyrosine (amino acid) sidechains to me, both of which have a benzene ring at the core. (For the record, there is also something called neutron crystallography, which works like X-ray crystallography except it's the nuclei that diffract, not the electron clouds - which allows you to visualize hydrogen atoms more directly, and even resolve the difference between hydrogen and deuterium. But it's another speciality technique, in part because neutron sources are so much weaker.) EDIT: since I actually did some work on visualizing electron density maps on the web, here's an interactive view of an older X-ray structure (from 2003, at only 3Å resolution) that shows how a protein molecule fits into the density: http://natechols.github.io/xtal.js/map_viewer.html http://natechols.github.io/xtal.js/map_viewer.html (click and hold the middle mouse button to pan through the molecule)
- mncharity 6y ago
  > computer generated imagery to define the “surface” of an atom The grids are isosurfaces of electron density. Analogous to isolines on a map illustrating mountain terrain height. Atoms are sticky little fuzzy balls. The fuzz, electron density, falls off exponentially. They don't have an "edge" in a non-fuzzy-object sense. Analogous to a stereotype volcano having an arbitrary perimeter. Where would I place it? Where you need climbing gear? Where biking up gets hard? In the foothills? Somewhere on the sloped plain? You place the perimeter wherever is convenient for what you're trying to use it for. People are usually interested in the densities between sticking atoms, which are several orders of magnitude down from peak density. Analogous to drawing an isoline at "the towering volcano is here high enough to start stubbing your toe on it". The picture draws isosurfaces of electron density at something like "around here one atom would 'bump' another, and you can see bonds" and at "I wrap a single atom only, but still have an interesting shape". To show the various features of interest, one draws multiple isosurfaces. As with a terrain map. But an exponential electron density scale is harder to represent than linear height scale. And it's hard to clearly draw more than a couple of nested 3D isosurfaces. So instead of placing many iso's at linear steps, here there are just a couple, more like an order of magnitude apart.
  - natechols 6y ago
    The terrain analogy is great - this is how the first structural biologists had to view electron density: https://image.slideserve.com/105608/electron-density-maps-of-proteins-sperm-whale-myoglobin-2-4-angstrom-resolution-l.jpg https://image.slideserve.com/105608/electron-density-maps-of... I think this is a stack of 2d "slices" through the density, printed on transparencies. But I've also seen 2d representations of charge density (some of which is just theoretical studies) that are even more similar to a terrain map.
    - mncharity 6y ago
      Neat. I've been exploring visual representations of electron density, optimized for educational use with XR. Intending to illustrate that science education content could be made transformatively less wretched. Isosurfaces and nonlinear color gradients are educationally problematic. And fuzz gradients are hard to visually stereo fuse. And on near-term AR displays, black is transparent, and background environment colors can't be manipulated, which limits the space of attainable colorizations. My current thought is to approach it as a volumetric light source. Composed of several linear scales, each a different color, with density as transparency. And respecting their true density when combined, so higher density scales "shine through" lower. We'll see. Maybe overlay random sample "sparkles" to maybe improve sense of spatial extent. I've not seen much similar work. If you know of any, I'd love to hear of it. Also, it seems there was a push some years back to emphasize electron density when teaching intro chemistry. A push that doesn't seem to have gelled. I've guesses, but I'd value thoughts on why.
- voxelghost 6y ago
  The nucleus is on the scale of 10e-5 (1/100,000) to the size of the whole atom (cloud).
  - Koshkin 6y ago
    Yet, the maximum density of the electron cloud (at least in the case of s-orbitals) is right inside it. (Talk about the "size of the whole atom"!)

pas 6y ago

Very good question. It'd be great to understand how this whole imaging process works. I have no idea, but it seems it involves many photos and rotation, and then DSP. So it's like CT for proteins .. maybe. It's like the x-ray crystallography but instead of repeating the x-ray many times on many-many samples. (edited) https://kpwulab.wordpress.com/2018/12/13/a-1-96-a-cryoem-map-of-mouse-apo-ferritin-determined-by-kps-group/ https://kpwulab.wordpress.com/2018/12/13/a-1-96-a-cryoem-map... https://cryoem.med.ubc.ca/image-gallery/ https://cryoem.med.ubc.ca/image-gallery/ https://cemas.osu.edu/news/2019/03/exciting-cryo-em-updates https://cemas.osu.edu/news/2019/03/exciting-cryo-em-updates https://elifesciences.org/articles/25648.pdf https://elifesciences.org/articles/25648.pdf

natechols 6y ago
Not many samples, many copies of the protein in what is often a single crystal (although if it's easily damaged, you might to use multiple crystals and combine the data post-processing). EM is actually very destructive, so they have to take thousands of micrographs of different individual molecules, and average them together.
- pas 6y ago
  Oh, okay, thanks! I've edited my comment to be hopefully less wrong. So it's like the x-ray version, just a different approach / energy scale? Or is that comparison ... doesn't make sense?
  - natechols 6y ago
    Both techniques give you the average electron density over thousands to billions of molecules. The difference is in what kind of data you actually collect, and how you process and combine the data to get that averaged map: - In X-ray crystallography, you're collecting the amplitudes of the Fourier transform of the electron density in the repeating unit of the crystal. The fact that it's a well-ordered (usually) crystal effectively "amplifies" the FT, and you get a series of images like this (from one orientation of the crystal): https://cdn.britannica.com/02/147302-050-3F732246/X-ray-diffraction-pattern-enzyme.jpg https://cdn.britannica.com/02/147302-050-3F732246/X-ray-diff... - In EM, you're collecting direct images of particles randomly distributed on a grid, but they're 2D and individually very noisy, like this: https://www.pnas.org/content/pnas/110/45/18037/F3.large.jpg?width=800&height=600&carousel=1 https://www.pnas.org/content/pnas/110/45/18037/F3.large.jpg?... In either case, there's a lot of complex math that goes into reconstructing the electron density - but the end result, the electron density map, is very similar (aside from the absence of crystal packing interactions in the EM map).