Figure 1:  A novel metric deducing the resolution of ab initio shape reconstructions from scattering data from the variability of the restored shapes (Tuukkanen, Kleywegt & Svergun, 2016).

Figure 1: A novel metric deducing the resolution of ab initio shape reconstructions from scattering data from the variability of the restored shapes (Tuukkanen, Kleywegt & Svergun, 2016).

Figure 2: A zig-zag SAXS shape of a multidomain repeats-in-toxin RTX CyaA protein reveals a ratchet mechanism preventing its backsliding upon translocation through “channel-tunnel” ducts (Bumba et al. 2016).

Figure 2: A zig-zag SAXS shape of a multidomain repeats-in-toxin RTX CyaA protein reveals a ratchet mechanism preventing its backsliding upon translocation through “channel-tunnel” ducts (Bumba et al. 2016).

The Svergun group places particular emphasis on hybrid approaches combining SAXS with X-ray crystallography, NMR spectroscopy, electron microscopy and computational methods to elucidate macromolecular structure and conformational transitions in solution.

Previous and current research

Small-angle X-ray scattering (SAXS) reveals low-resolution (1-2 nm) structures of biological macromolecules and functional complexes in solution. The resolution and reliability of SAXS-based structural models have increased tremendously over the past decade. Subsequently, there has been a significant growth in use in biological SAXS techniques in the scientific community worldwide.

Our group leads the development of novel computational methods for SAXS data analysis and interpretation. We have developed methods for ab initio shape reconstructions from SAXS data, which is now widely used in the community. More recently, responding to the community’s needs, we proposed a method for assessing the resolution of these models (Figure 1). Particular attention in our work is given to the joint use of SAXS with other methods including crystallography, NMR, electron microscopy and bioinformatics in hybrid modelling approaches. We developed the world’s most used SAXS program package, ATSAS, employed by more than 12,000 users from more than 50 countries.

Our group operates and maintains a dedicated high brilliance synchrotron beamline – P12 – at DESY’s third generation storage ring, PETRA III. P12 has a robotic sample changer for rapid automated experiments, and possesses a data analysis pipeline for building structural models online. The beamline offers options for remote access, as well as an in-line purification setup using size exclusion chromatography with parallel biophysical and SAXS measurements.

In collaborative projects with the users from the ever-growing SAXS community, group members offer advice on sample preparation and provide help with data collection, analysis and structural modelling. SAXS is employed to study overall structural organisation of macromolecules and conformational transitions and to quantitatively characterise oligomeric mixtures, intrinsically unfolded proteins, hierarchical systems and other objects of high biological and medical importance (Figure 2).

Future projects and goals

The present and future work of the group includes:

  • Further methods development for the reconstruction of macromolecular structure from X-ray and neutron scattering.
  • Hybrid applications of SAXS with crystallography, NMR, electron microscopy and bioinformatics to construct and validate structural models.
  • Participation in collaborative SAXS projects at the P12 beamline.
  • Further extension of P12 capabilities including time-resolved and anomalous scattering techniques as well as ultra fast data acquisition combined with new multi-layer optics for high-brilliance X-ray experiments.