Cryogenic electron microscopy (cryoEM)

This technique has managed to determine protein 3D structures for proteins that people were not able to crystallize for X-ray crystallography.

It is said however that cryoEM is even fiddlier than X-ray crystallography, so it is mostly attempted if crystallization attempts fail.

By looking at Figure 85. "Image showing This is the type of image that you get out of a raw CryoEM experiment.", you can easily understand the basics of cryoEM.

We just put a gazillion copies of our molecule of interest in a solution, and then image all of them in the frozen water.

Each one of them appears in the image in a random rotated view, so given enough of those point of view images, we can deduce the entire 3D structure of the molecule.