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Finding drug candidates faster
SARomics Biostructures in collaboration with the BioMAX beamline’s scientists successfully tested the feasibility of serial crystallography at MAX IV. The advent of the first fourth-generation synchrotron pioneered by MAX IV finally makes serial crystallography more easily accessible to private companies.
Crystals for drug development
SARomics Biostructures is a contract research organization (CRO) offering structural biology services in the field of early-stage drug discovery. One of SARomics’s core expertise is protein X-ray crystallography performed using synchrotron light. Using this technique, SARomics offers protein structural analyses crucial for the development of new drug candidates. Using the high-quality X-rays produced at MAX IV, the first fourth-generation synchrotron, researchers can now perform so-called “serial crystallography” experiments previously possible only at a handful of facilities relatively inaccessible to commercial entities. The use of MAX IV’s photons for such experiments allows SARomics to significantly improve and expand the service it provides to its clients.
The many challenges of X-ray crystallography
X-ray crystallography is the gold standard for the characterisation of biological structures, and researchers use it to observe the structures of protein complexes and their ligands. One drawback of standard synchrotron X-ray crystallography is that the size of the crystal partially determines the quality of data that can be collected. The smaller the crystal, the poorer the data. This is particularly problematic for a company like SARomics since some of the most important targets for their customers’ drug design activities are membrane proteins, which typically produce very small crystals.
The use of serial crystallography can help overcome the crystal size problem. Serial crystallography involves collecting segments of data from tens of thousands of microcrystals and assembling the data using advanced computer software. Synchrotrons of older generations cannot provide this technique, and until now researchers had to resort to X-ray free-electron laser (XFEL) facilities. Unfortunately, access to XFEL facilities is relatively difficult, especially for private companies, due to extremely high running costs and high competition for beamtime. A solution is now coming from a new generation of synchrotron facilities.
New opportunities at 4th-gen synchrotrons
Fourth-generation synchrotrons pioneered by MAX IV can help solve the scarcity of opportunities for serial crystallography experiments. The higher quality of X-rays produced at the Swedish national synchrotron can be used to run serial crystallography experiments that are simply not possible in older facilities, making it simpler also for companies to perform this technique. To put MAX IV’s capabilities to the test, SARomics researchers went to the BioMAX beamline and analysed a total of 15 555 crystals of a small protein mounted on different kinds of support. The quality of the obtained data was comparable to that of data collected using conventional methods. This pilot project proved that serial crystallography at MAX IV is readily applicable to industrial projects, with significant benefit for SARomics’s operations.
“The main benefit of this pilot project for SARomics was that our staff learned valuable new data collection methods that extend the range of techniques we can offer, enhancing our attractiveness in a competitive market.”Derek Logan, SARomics Biostructures
SARomics Biostructures AB