Proteins are biological molecules that perform almost all biochemical tasks in all forms of life. In doing so, the tiny structures perform ultra-fast movements. In order to investigate these dynamic processes more precisely than before, researchers have developed a new algorithm that can be used to evaluate measurements at X-ray free-electron lasers such as the SwissFEL more efficiently. They have now presented it in the journal Structural Dynamics.
Sometimes, when using the navigation system while travelling by car, the device will locate you off the road for a short time. This is due to the inaccuracy of the GPS positioning, which can be as much as several metres. However, the algorithm in the sat nav will soon notice this and correct the trajectory displayed on the screen, i.e. put it back on the road.
A comparable principle for addressing unrealistic motion sequences has now been successfully applied by a team of researchers led by PSI physicist Cecilia Casadei. However, their objects of investigation are about a billion times smaller than a car: proteins. These building blocks of life fulfil crucial functions in all known organisms. In doing so, they often perform ultra-fast movements. Analysing these movements precisely is crucial for our understanding of proteins which can help us produce new medical agents, amongst other things.
How to “film” proteins…
To further improve the understanding of protein movements, Casadei, together with other PSI researchers, a researcher at DESY in Hamburg and other colleagues at the University of Wisconsin in Milwaukee, USA, has developed an algorithm that evaluates data obtained in experiments at an X-ray free-electron laser (XFEL). An XFEL is a large-scale research facility that delivers extremely intense and short flashes of laser-quality X-ray light. Here, a method called time-resolved serial femtosecond X-ray crystallography (TR-SFX) can be used to study the ultra-fast movements of proteins.
The measurements are very complex for several reasons: the proteins are much too small to be imaged directly, their movements are incredibly fast, and the intense pulse of X-ray light of an FEL completely destroys the proteins. On the experimental level, TR-SFX already solves all these problems: no individual molecule is measured, but rather a large number of identical protein molecules are induced to grow together in a regular arrangement to form protein crystals. When the FEL X-ray light shines on these crystals, the information is captured in time before the crystals and their proteins are destroyed by the pulse of light. The raw data from the measurements are available as so-called diffraction images: light spots that are created by the regular arrangement of the proteins in the crystal and registered by a detector.
Read more on the PSI website
Image: Physicist Cecilia Casadei was part of an international team that developed a new analysis algorithm. With their method, called “low-pass spectral analysis”, the data collected when proteins are measured at X-ray free-electron lasers can be evaluated more efficiently than before.
Credit: Paul Scherrer Institute/Mahir Dzambegovic