Identification of Protein Explosions with X-ray Laser
Illustration of the protein Calmodulin when it explodes when it is irradiated by an X-ray laser pulse. The image shows the orbit of the atoms from the original positions in the protein. Image: Carl Caleman.
Uppsala researchers have used a new method to identify proteins by observing how the proteins explode when one irradiates them with very intensive X-ray pulses. The new research results may play an important role for future development of new medicines through greater knowledge about proteins’ shape and structure.
When individual proteins are irradiated by an X-ray laser with ultra-short pulses, on the femtosecond scale (10-15 s), with high intensity, they are ionised and a lot of electrons are released, leading to an explosion of the protein.
When previously examining proteins with X-ray lasers, it has been important to be able to take a picture of proteins before they are destroyed by the explosion. But now, researchers at Uppsala University have developed a method where they have been able to show that atoms and ions which are irradiated by an X-ray laser keep a part of the original information about their structure even after they have exploded.
In the study, the researchers have examined how various secondary structures, or foldings, of proteins differ when they explode when they were irradiated by an X-ray laser. In total, three different pairs of proteins, where each pair shows different kinds of similarity in their structure were examined.
The pattern of the ions from the explosion of the protein MS2, as they potentially could be detected. Image: Tomas André.
The energy released at the irradiation makes the protein explode and leaves a unique fingerprint for each protein on an imaging detector. With the help of computer simulations, the researchers could then follow and analyse how the three proteins and their foldings exploded depending on where on the detector they ended up.
– The fingerprint is like a 2D image, looking like a map of the world, showing in which directions the ions in the protein went depending on where they end up on the map. We simply count how many ions end up in a pixel. Some pixels have more information than others, depending on how many ions ended up there, says Tomas André, doctoral student at the Division of X-ray Photon Science at the Department of Physics and Astronomy and first author of the article.
The method may be a good complement to traditional techniques for imaging individual proteins. It may also be combined with machine learning to improve the accuracy and reliability in determining protein structures.
– The next step is to test the method with experimental examinations at an X-ray laser. There are X-ray lasers is Hamburg at FLASH or EuXFEL which we plan to use to test how various proteins can be detected, says, Carl Caleman, professor at the Division of X-ray Photon Science at the Department of Physics and Astronomy.
The new research results may in the future play an important role for the development of new medicines by complementing traditional imaging techniques and give a greater knowledge about the shape and structure of proteins.
Camilla Thulin
English translation: Johan Wall
Article Reference
Tomas André, Ibrahim Dawod, Sebastian Cardoch, Emiliano De Santis, Nicusor Timneanu, and Carl Caleman. Protein Structure Classification Based on X-Ray-Laser-Induced Coulomb Explosion, Phys. Rev. Lett. 134, 128403 – Published 27 March, 2025. DOI: https://doi.org/10.1103/PhysRevLett.134.128403
The study has been made at Uppsala University and was funded by the Swedish Research Council and EU Horizon.
Contact
Carl Caleman, professor at the Division of X-ray Photon Science, Department of Physics and Astronomy, carl.caleman@physics.uu.se, +46729999425