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X-ray free electron lasers such as LCLS have been revolutionary in structural biology, allowing unique experiments on many different types of molecules.


The promise of the X-ray free electron laser

Al Baker, former Area Manager for Accelerator Systems, inside the SLAC linear accelerator, or linac, in 2002.
Al Baker, former Area Manager for Accelerator Systems, inside the SLAC linear accelerator, or linac, in 2002. At two miles long, the linac was the world's longest linear accelerator and could accelerate electrons to 99.9999999% of the speed of light.

Shortly after scientists from the SLAC National Accelerator Laboratory proposed to drive the Linac Coherent Light Source, the potential of these novel X-ray light sources for structural biology became clear.

With the help of molecular dynamics modeling, it was shown that the ultrafast X-ray pulses from an X-ray Free Electron Laser (XFEL) such as LCLS could be used to record high-resolution X-ray diffraction data from proteins before the majority of X-ray radiation damage takes place (a principle known as “diffraction-before-destruction”).

After the world’s first XFEL started running in 2009, the first teams rapidly succeeded in providing a proof of principle for protein crystallography using femtosecond X-ray pulses. Only 3 years after LCLS came online, it was shown that the XFEL can be used to determine atomic resolution structures from protein microcrystals.

Today, several instruments are available at LCLS to determine macromolecular structures, study time-resolved dynamics or perform challenging spectroscopy experiments.

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Impact of X-ray free electron lasers in biological sciences

Since LCLS came online in 2009, the XFEL has made a large impact in diverse areas of structural biology.

The intense, ultrafast X-ray pulses have allowed the study of radiation-sensitive macromolecules (including metalloproteins) and targets that are difficult to crystallize, including many medically relevant membrane proteins. LCLS has also enabled the study of time-resolved protein dynamics, providing scientists with molecular movies of macromolecules in action.

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