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Development of analysis methods for scattering studies of biological systems

Dmitri I. Svergun, European Molecular Biology Laboratory, Hamburg Outstation c/o DESY, Hamburg, Germany

2019.05.21 | Trine Møller Hansen

Date Tue 18 Jun
Time 15:10 15:35
Location iNANO AUD (1593-012), Gustav Wieds Vej 14, 8000 Aarhus C

Dmitri I. Svergun, European Molecular Biology Laboratory, Hamburg Outstation c/o DESY, Hamburg, Germany

Development of analysis methods for scattering studies of biological systems

Small-angle scattering (SAS) of X-rays and neutrons (SAXS and SANS) is widely used to study non-crystalline systems of different nature, including solutions of biological macromolecules [1]. The method reveals low resolution structures of native particles and complexes and elucidates the structural changes in response to variations in external conditions. The scattering patterns from the dissolved macromolecules are rotationally averaged due to their chaotic orientations in solution limiting the information content in the data. Robust data interpretation and modelling methods are therefore of major importance for broad applications of solution scattering in biology. In the present talk, remarkable progress in data analysis approaches over the last decades, which was accompanied by the instrumental developments [2] will be considered and illustrated in applications to various biological systems.

Low resolution macromolecular shapes can be reconstructed ab initio from the SAS data providing information about the overall particle structure. Further, hybrid applications with high resolution methods like crystallography and NMR, but also with complementary biophysical and biochemical techniques, allow one to build yet more detailed models. In particular, validation of predicted or experimental high resolution models in solution and identification of biologically active oligomers are possible. Quaternary structures of complexes can be analyzed by rigid body modeling of individual subunits/domains, if their models are available. SAS can also be applied to characterize the solution states of partially or fully flexible macromolecules including intrinsically disordered proteins.

Of special interest and importance are joint SAXS and SANS applications. The absence of radiation damage and the possibility of contrast variation by solvent exchange (H2O/D2O) or by specific deuteration makes SANS an extremely useful complementary method to SAXS. Joint applications of SAXS and SANS for the structural characterzation of macromolecular solutions, including data analysis techniques for simultaneous interpretation of X-ray and neutron scattering patterns and their applications [3,4] will be presented. Future perspectives of the synergistic use of SAXS/SANS with other techniques in structural biology will be outlined.

References:
1. Svergun DI, Koch MHJ, Timmins PA, May RP. (2013) Small angle X-ray and neutron scattering from solutions of biological macromolecules, Oxford Univ. Press. 358 pp.
2. Tuukkanen AT, Spilotros A, Svergun DI. (2017) IUCrJ, 4, 518-528.
3. Svergun DI, Pedersen JS, Serdyuk IN, Koch MH. (1994) Proc Natl Acad Sci USA. 91, 11826-30.
4. Niemann HH, Petoukhov MV, Härtlein M, Moulin M, Gherardi E, Timmins P, Heinz DW, Svergun DI. (2008) J Mol Biol. 377, 489-500.


The lecture is part of the symposium Recent progress in small-angle scattering from soft matter and biological systems on the occasion of Professor Jan Skov Pedersen's 60th birthday.     

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