An algorithm for sharper protein films

Date:
May 30, 2023
Source:
Paul Scherrer Institute
Summary:
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.


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FULL STORY ========================================================================== 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.

... and how to evaluate the measurement data Where the experimental
challenges have been overcome, the evaluation of the data is just
beginning. "The measurement of each individual crystal provides only
two percent of the data of a complete image." This incompleteness has
physical and experimental reasons and can only be eliminated by combining
the measurement data of many crystals in a meaningful way. Casadei's
research focuses on exactly how to go about this.

The method established so far is called "binning and merging." "A lot has
been achieved with this method in the last decade," says Casadei. With
this method, the data are divided into time intervals and all data
within one interval, a "bin," are averaged. However, a lot of detailed information is also lost in this averaging. "You could say that the
individual images of the protein film are then all a bit washed out,"
Casadei continues. "That's why we have developed a method that allows
us to get more out of the measurement data." The new method devised
by Casadei and her colleagues is called "low-pass spectral analysis,"
or LPSA for short. "Similar to electronics or audio technology, we apply
a low-pass filter," Casadei explains. "However, in our case it comes in
the form of advanced linear algebra. We apply these formulas to remove
unwanted noise from the data without losing the relevant details."
In short and simple terms, the raw data, i.e. the diffraction images of
the protein crystals, are tracked throughout the protein motion. This
movement is assumed to be smooth, i.e. jerk-free. Similar to how the
navigation system corrects itself when the car seemingly leaves the
course of the road, the new algorithm by Casadei and her colleagues
mitigates errors of the protein movement reconstruction.

HDR for protein films Lay people may not notice an immense difference
in the new protein films. But for the cineastes at X-ray free-electron
lasers, the improvement is comparable to switching from a DVD film to
HDR quality.

"Above all, the new algorithm now allows researchers here at
SwissFEL at PSI to extract more information from their data," says
Casadei. Conversely, this means the algorithm can help shorten long
measurement times. Since beam time is always in high demand at large-scale research facilities, and in particular at SwissFEL, this is a most welcome prospect for protein researchers using this highly advanced facility.

* RELATED_TOPICS
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* RELATED_TERMS
o Electron_microscope o Robot o Protein o Machine o
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========================================================================== Story Source: Materials provided by Paul_Scherrer_Institute. Original
written by Laura Hennemann. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Patrick Sharman, Alastair J. Wilson. Genetic improvement of
speed across
distance categories in thoroughbred racehorses in Great Britain.

Heredity, 2023; DOI: 10.1038/s41437-023-00623-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230530125358.htm

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