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Electron Microscopes Close To Imaging Individual Atoms

Posted by timothy on from the it's-down-there-somewhere-let-me-take-another-look dept.

An anonymous reader writes with this excerpt from Science: Today's digital photos are far more vivid than just a few years ago, thanks to a steady stream of advances in optics, detectors, and software. Similar advances have also improved the ability of machines called cryo-electron microscopes (cryo-EMs) to see the Lilliputian world of atoms and molecules. Now, researchers report that they've created the highest ever resolution cryo-EM image, revealing a druglike molecule bound to its protein target at near atomic resolution. The resolution is so sharp that it rivals images produced by x-ray crystallography, long the gold standard for mapping the atomic contours of proteins. This newfound success is likely to dramatically help drugmakers design novel medicines for a wide variety of conditions.

5 of 55 comments (clear)

  1. Nice but... by Anonymous Coward · · Score: 5, Informative

    While cryo-EM is really a big step forward the summary make it sound like it's the first time EMs can image atoms, that is not really the case at all. HRTEM (high resolution tunneling electron microscopes) have even better resolution that 0.2 nm, one order of magnitude better even ( eg. http://journals.aps.org/prl/abstract/10.1103/PhysRevLett.102.096101 ). It's also worth noting that the applications and use cases are very different for cryo-EM and HRTEM.

    1. Re:Nice but... by the+gnat · · Score: 4, Informative

      There's another technical objection to the summary: "atomic resolution" in this context isn't the same thing as "imaging individual atoms". The actual cryo-EM images themselves are much noisier and do not have nearly this effective resolution - it is the average of many thousands of images that gives you atomic resolution electron density maps. (The same is true for X-ray crystallography, although you start with just Fourier amplitudes there, not images.) That's not a slam on the paper, which is an impressive technical achievement, but as the authors note, many conformationally homogeneous single particles (i.e. protein complexes) are required to get a map of this quality. Any differences between particles will simply be averaged out, and the more different they are, the worse the resolution.

    2. Re:Nice but... by the+gnat · · Score: 4, Informative

      I really do hope the people doing this have examined and discussed the possible pitfalls of drawing conclusions from averages of this type of data.

      Yes, the pitfalls are well known, mostly because this has always been an issue with crystallography as well - it is impossible at present to determine the 3D molecular structure from a single molecule, so we are always dependent on either crystalline diffraction or averaging thousands of images to obtain the density map. (NMR has its own, well-understood problems.) The good news is that we known enough about macromolecular structure to be able to make subjective judgements very quickly based on the level of detail in the maps. (There are also plenty of higher-resolution structures of many smaller components, so we can calibrate our expectations based on known parts.) If the molecules are very heterogeneous, or the averaging is done poorly, the maps will not display known high-resolution features such as secondary structure or amino acid sidechains. For crystallography, there are also ways to calculate the deviation from the average (and I presume EM either has something analogous, or will soon). It is also common for some regions to have higher "local resolution" than others, and this can be quantified in various ways.

      These methods still lose information - if, say, 10% of copies of a particular loop or sidechain are in a different conformation, this will probably not be captured. But EM experts have gotten much better about identifying clusters of similar conformations, at least on a larger scale. And in the end, the static average structure is still vastly more useful than no structure at all. Scientists can and do still publish spectacularly stupid interpretations occasionally, but these aren't due to the misuse of averaging, but rather to pure incompetence and wishful thinking.

  2. this technology has been in use for years by crgrace · · Score: 4, Informative

    This is not a worthy story. Cryo-EM is a fast growing, exciting field but higher resolution electron microscopes that what this article trumpets have been available for years. For example, the TEAM microscope built in 2008 at Lawrence Berkeley National Lab has a resolution of 50 pm:

    http://foundry.lbl.gov/facilities/ncem/expertise.html#team1

    I personally saw individual gold atoms deposited as a nanobridge on a graphene substrate. In 2010.

  3. Poor headline here and at the article; good piece by Anonymous Coward · · Score: 3, Informative

    The ability to image the atomic structure of an individual (fragile and 3-d) protein is still notable and the article gets this mostly right.
    But, yes: the 1986 Nobel prize went to developers of the TEM and STM that had both already achieved atomic resolution MANY years before. The first microscope to allow atomic resolution was the field ion microscope (in the 1950s!), but the inventor had died before the Nobel prizes were awarded.