Welcome to I04-1

I04-1 delivers a high-throughput approach similair to that pioneered in industry, where it is axiomatic that the best way to study ligand binding involves developing a well-diffracting crystal system, which allows for the rapid X-ray data collection necessary to observe the binding of the many compounds generated by medicinal chemistry.  The implication for a beamline is that flexibility is less important than stability and speed. I04-1 is heavily utilised by the XChem platform, as well as being fully availiable to the MX user community for rotational cryogenic experiments.

The research focus is on taking high-throughput approach to its logical extreme, namely all aspects of implementing and exploring routine medium- throughtput fragment screening by crystal structure.  This involves a lot more than just the X-ray experiment, and since late 2012 the beamline has been partnered with the Protein Crystallography group, now at the Centre for Medicince Discovery in University of Oxford.

Developments include:

• Academic and Industrial access to high throughput crystallogrpahic screening
• Rapid synthesis of compounds using automated robotics platforms
• Fragalysis platform - Quick review of Crystallographic fragment data for advancing medicinal chemistry of screened targets
• Development of algorithms for hit identifentifaction in crystallographic screens: Pan-Dataset Density Analysis (PanDDA)
• Development of room temperature crystallographic fragment screening

Please discuss your requirements with a member of the beamline team before your experiment.

I04-1's wavelength is fixed at the Bromine K edge (E = 13530 eV, λ = 0.9163 Å), where a strong anomalous signal can be measured for most commonly-used heavy atom derivatives (see figure).  SAD is usually very effective here - unsurprisingly: thanks to modern detectors and phasing algorithms, tunability is essential only for special cases, especially if the experiment is done carefully (see e.g. Krojer, Pike, von Delft, Acta D 2013)

Estimated anomalous difference at 0.92Å resolution for common elements.  These were calculated assuming:  for all elements, 1 fully occupied heavy atom site per 300 residues;  for Se, 1:42 heavy atoms:residue;  and using the formula derived from Smith, J., Curr. Opin. Struct. Biol. vol1, p1002 (1991).