Schneider (Thomas) Group

Figure 1: Rigid regions (centre; blue and green) identified from ensembles of structures can be used for superposition and subsequent analysis (left) or as fragments to interpret experimental data from methods with lower resolution than X-ray crystallography (right).

The Schneider group is operating two beamlines for macromolecular crystallography at the PETRA III synchrotron and develops new methods for structure determination.

Previous and current research

During the past six years, we built three beamlines at the new PETRA III synchrotron in close collaboration with the Cipriani and Fiedler teams. Since 2012, the beamlines for small angle X-ray scattering on solutions (SAXS) and X-ray crystallography on crystals of biological macromolecules (MX) are open for users. The beamlines are embedded in an Integrated Facility for Structural Biology that supports non-specialists in taking a project from producing a suitable sample to determination of the structure by SAXS and/or MX.

Partly due to the enormous progress in synchrotron radiation-based structural biology, structural data on biological macromolecules are produced at an ever-increasing rate, creating the need to develop tools for efficient mining of structural data. We are developing tools for which the central concept is to use coordinate errors throughout all calculations. The necessity of this approach becomes clear when one considers that in contrast to sequence data, where a nucleotide entry can only be right or wrong, the precision in the location of an atom in a crystal structure can vary over several orders of magnitude. While the position of an atom in a rigid region of a protein giving diffraction data to high resolution may be known to within 0.01 Å, for an atom in a flexible region of a poorly diffracting protein the coordinate error may reach more than 1.0 Å.

From a technical point of view, extracting information from large amounts of raw structural data (as many as hundreds of structures containing thousands of atoms each) is a very complex task and requires sophisticated algorithms, both for the analysis and for the presentation and 3D visualisation of the results.

Future projects and goals

We will continue the commissioning work on the new beamlines and strengthen the user programme to full capacity. The two beamlines for macromolecular crystallography will offer excellent conditions for data collection on small (micron-sized) crystals, crystallographic phasing, and the development of new experimental protocols for challenging systems.

On the computational side, we will work on improving the error models underlying our methods and on expanding our computational framework using genetic- and graph-based algorithms. We also plan to use recurrent structural fragments extracted from ensembles of structures as search models in molecular replacement and for the interpretation of low-resolution electron density maps. This aspect of our computational work will be very helpful in the interpretation of experimentally phased electron density maps obtained on the PETRA III beamlines.

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