Deciphering the structure of biomolecules

Using the X-ray flashes of the European XFEL, scientists can decipher the 3D structure of biomolecules, cell constituents and whole viruses. This will provide the basis for future medicines.

Today already, scientists can analyse the structure of biomolecules in detail. The X-ray radiation sources used for these investigations are too weak, however, to allow single molecules to be studied. Instead, the researchers first have to grow crystals in which the molecules are aligned in regular order. These crystals can then be used for a “group picture” in which the individual images reinforce one another enough to create a usable result. The problem is that crystallization is not possible for many relevant biological substances – many molecules, molecule complexes, cell membranes and whole cells are thus left out.

 

Ribosom

Ribosomes are large molecular complexes that act as "protein factories" and occur in every cell. The X-ray laser opens up completely new opportunities to decipher such biological structures with atomic resolution without the need for the extra step of tediously growing them into crystals first.

(MPG)

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Explosion of a biomolecule

Biomolecules are destroyed by intense X-ray radiation: they "explode". The illustration shows a simulation of this process. In order to obtain a usable image of the biomolecule, the image must be recorded very quickly before the sample is destroyed.

(© DESY)

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Completely new opportunities

The European XFEL opens up completely new opportunities in this respect. Its X-ray flashes are so intense that scientists can also use small crystals of bad quality or even do away with crystallization altogether. In addition, the duration of the flashes is so short that the molecule hardly changes during the exposure. The molecule starts to decay – due to the enormous forces generated by the strong incident light – only after the X-ray flash has passed the sample and the picture of the atomic structure has been taken.

These possibilities to study biomolecules using flashes of X-rays are so unique and new that until now, there have been only theoretical calculations and simulations on the subject. Experiments at the XFEL pilot facility FLASH at DESY, however, brilliantly confirmed the method. But the challenges that have to be overcome are still enormous and require an interdisciplinary approach. Biologists, physicists and mathematicians are already collaborating closely to solve these problems.

With this method, the European XFEL offers completely novel possibilities to create images of larger biological structures such as single viruses in atomic detail. Special emphasis will be put on viruses that cannot be crystallized – for instance the viruses responsible for AIDS and herpes.

Additionally, the ultrashort X-ray flashes make it possible to follow the motion of molecules from instant to instant, enabling scientists to study e.g. functional processes at cell membranes. Such investigations will lead to new insights into the progress of infections at the molecular level, and thus represent an essential basis for the development of new medicines.