[benjaminva]

I had the privilege to ocasionally work with Holger Stark on similar structure determination challanges and can confirm that they really pushed the limits here thanks to very smart statistical methods. The resolution heavily depends on correctly sorting/classifying the large amount (> 10k for sure) images of these small particles.

There exists a race in the structural biology community about the next big method that allows to determine structures of proteins that were hard to crystalize and it seems that CryoEM is becoming the winner in this race.

As an alternative approach, people are building large X-ray lasers that have extremly high intensity and short pulse lengths which they plan to shoot at single particles and resolve individual scattering images. This method can very likely also achieve atomic resolution of non-crystaline particles, even without the need to freeze them down.

It will be exciting times for the whole bio-chemical physics community. Congrats to Holger and the team for another great publication in Nature.

[natechols]

Having worked in X-ray crystallography on synchrotrons and XFELs, I can't take the single-particle XFEL concept seriously any more. Ten years ago it seemed impressive, but the EM technology has advanced so much faster - and it's a fraction of the cost. There are some neat applications of nanocrystallography, but that too seems like a niche application now, not a magic bullet for accelerating protein structure determination.