First 3D images of a virus

The assembled three-dimensional diffraction space. (a) The first ten patterns are shown in their best recovered orientations. Each diffraction pattern represents a slice through the squared modulus of the 3D Fourier transform of the electron density. (b) All 198 diffraction patterns plotted with a section cut out to show the central part of diffraction space. Diffraction symmetry and object symmetry can be directly recovered from the measured diffraction data in the EMC process. Credit: Stanford LCLS - Physical Review Letters

People were awed at the discovery of the molecule of Life, the DNA. Scientists and technologists were awed by the way it was discovered, through x-ray crystallography. Rosalyn Franklin was the chemist expert in x-ray crystallography that provided Watson and Crick the images leading to the understanding of the double-helix and its role in coding the instruction of life. 
Seeing a molecule is of paramount importance in understanding it, particularly in biology. In biology molecules combine based on their shape and knowing the shape leads to an understanding of their interactions and their potential interaction.

Since those early days x-ray crystallography has made great progress and now we know the shape of thousands of proteins. However, many more are yet unchartered.

The reason is the x-ray crystallography, not surprisingly given the name, works only if you deal with crystals. When you want to discover the shape of a protein the first thing you need to do is to create a crystal, then you can x-ray it.  Unfortunately, most proteins and for sure more complex structures do not crystallise. 

Here is where this news from Stanford, published in Physics, comes in.

The reason why you need a crystal is to keep the molecule stable as you "photograph" it using x-rays. In a crystal molecules are strongly tied one another and don't move. By photographing it from different points of view you can create a 3-D image.  It is intuitive that you can't do that if the molecule moves as you take the various photos.

By using a lot of software researchers at Stanford have been able to reconstruct the 3D shape of a molecule even if that molecule bounces around. Clearly they need to take many more photos and then like in a gigantic puzzle try to find points that coincides to re-orient all the other points. 

The photos are not real photos like the one you can take of your dog. They are recording the diffraction patterns created on the x-ray beam as it hits a molecule. It is more like a shadow, than a picture. The brighter (more energetic) the x-ray the stronger the shadow and the diffraction pattern. At the same time the stronger the x-ray beam the more probable that it will shatter the molecules. If that happens you won't be able to take a second picture!

Hence the solution of the researchers (that need to have a strong shadow to identify overlapping points) was to use femtoseconds pulses of x-ray. The shadow is good because the energy of each pulse if high, but the overall energy is below the thresholds that would lead to the crumpling of the molecules.

Amazing the ingenuity of the researchers and amazing what we can do with signal processing today!

Author - Roberto Saracco

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