Electron Density

What is an electron density puzzle?

Lately, we’ve been posting a series of Reconstruction puzzles using electron density, and in the last blog post in this series we discussed why Reconstruction puzzles are scientifically valuable. Today, we’ll be talking a bit more about the science behind electron density puzzles and their types.

Different types of lab experiments

In Foldit, we use the same name, “Electron Density” to describe two different types of experimental data. These two experiments are cryo-electron microscopy (cryo-EM) and X-ray crystallography, and they actually measure different things.

For crystallography, we use diffracted x-rays to measure the electron density, or in other words electron distribution, of the protein. Since electrons orbit the nucleus of an atom, the distribution of electrons shows us where the protein atoms are.

However, for cryo-EM experiments, “Electron Density” is actually a bit of a misnomer for the measurement. Instead, a better way to think of them is a map of the electron potential of the protein. Unlike the x-rays in crystallography, the microscope beam in cryo-EM is more formally interacting with charge in the protein. This means that the maps are slightly different. Thankfully, in Foldit we can treat both maps the same way when folding a protein.

In theory, we could someday even post maps that come from neutron crystallography, in which we measure the distribution of atomic nuclei, not the electrons. The difference in that case is that you tend to see the hydrogens in the protein, which usually are invisible in X-ray crystallography since they don’t have enough electron density. There are a lot of hydrogen atoms in a protein! We usually hide them in Foldit, but if you want you can change your Foldit View Options to Show all hydrogens.

X-ray crystallography vs. electron microscopy

The experimental procedure of how we get data from X-ray crystallography and cryo-EM is quite different, so not surprisingly there are also differences in how we process the data to produce maps for Foldit.

Scientists tend to solve X-ray crystal structures iteratively. After building a structure, they will recalculate the density map, then rebuild their structure, then recalculate the density map, then rebuild… This is because, weirdly, the working structure helps to clarify unknowns in the x-ray data. That means that the map actually gets clearer as the protein structure you’re working on gets better.

Cryo-EM is different in that the working structure does not affect the map at all. That means that iteration isn’t needed in the same way as in X-ray crystal structures.

The meaning of a map

In summary, Electron Density puzzles are a bit more complicated beneath the surface than we often show. Maps come from different types of experiments, which measure different qualities of a protein.

It’s important to realize that the map by itself doesn’t mean much for scientists until we have an atomic-level structure for the target protein. Building that structure is the crucial step, that’s where Foldit is needed most.

Foldit players have already shown a strong ability to solve Electron Density puzzles and resolve tough scientific problems for both crystallography and cryo-EM. In the future, we can expect even more Electron Density challenges as experimental techniques improve--especially in cryo-EM. We’re looking forward to seeing what Foldit players are capable of!

Written by horowsah and bkoep

( Posted by  agcohn821 51 644  |  Fri, 07/15/2022 - 14:43  |  0 comments )
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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
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