This theme promotes work that enables the scientific community to use and combine a range of structural biology methods.  With the new possibilities offered by MAX IV and ESS, and with rapid progress in the fields of macromolecular crystallography, Cryo-EM, small angle scattering and the use of XFELs, the scientists benefiting from these methods do not always know what the different possibilities are and how to best combine data from complementary structural biology techniques.  There is an urgent need for knowledge in how to exploit combined data from neutrons and X-rays to answer completely new research questions regarding macromolecular structure and function.





ISB WorkING Group 1

Biocompute AND Artificial intelligence & Machine learning

The Biocompute Working Group seeks to address several fundamental issues such as:

  • Novel and refined program packages are needed for new MX/neutron technologies (XFEL, neutron data from spallation sources, and much more)

  • Integration of state-of-the-art Applied Maths in existing software

  • Appropriate research education to better understand processes that links data to results.

  • A need to learn how to better use HPC more effectively than we do today.

  • A need to see, learn and integrate the potential for machine learning & AI-techniques in our analysis.

We focus our work on project oriented SB-users with complex scientific questions (multi-modular, dynamic, size and more), experimental infrastructure personnel/researchers, HPC personnel/researchers, user platforms and applied mathematicians and programmers.


TIME-resolved structural biology - new possibilities in a time of new facilities

Time-resolved structural biology aims at determining structural intermediates in order to understand the function of e.g. proteins. Work in the area of time-resolved crystallography, first at synchrotron sources and more recently also at X-ray Free Electron Lasers (XFELs) has shown that it is possible to study structural events down to very short time scales. One important development follows the fact that very small crystals can now be used. It makes it possible to trigger events with diffusion in much shorter time scales and to study irreversible reactions common in biology, which makes the time-resolved techniques potentially much more generally applicable.

Time-resolved crystallography must be complemented with other techniques, e.g. different spectroscopic techniques to verify that what happens in the crystal is the biologically relevant reaction. In a broader sense, other techniques such as XAFS, SAXS, neutron spectroscopy, NMR and molecular dynamics are important to give a more complete picture.

There are however challenges in time-resolved crystallography, for example: Finding the best way to trigger a reaction is an issue that has to be solved for each individual case, though there are general strategies that can be developed. Data sets are often assembled from multiple crystals, which are often heterogenous. Typically, there is only a fraction of the molecules in the desired state making it difficult to interpret the data. Collecting data while a reaction is taking place can lead to disorder in the crystal and loss of resolution.



Amyloid and amyloid type systems are implicated in a wide range of diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, type 2 diabetes mellitus, and a variety of transmissible spongiform encephalopathies. While extensive structural studies have been carried out on many amyloid forms, there remain major questions about the amyloid deposits associated with these pathologies and about the way in which they assemble. Generalised structural information derives from fibre diffraction, NMR (notably ssNMR), some single crystal information from short peptides, and more recently cryo-EM. Despite the major biomedical importance of this area, major challenges exist in all of these approaches, and the linkage between them is often poor or absent.

The working group aims to initiate a discussion forum amongst researchers working on amyloid using a wide range of different approaches ranging from molecular level approaches to imaging & clinical work. The topic therefore relates primarily to the LINXS mission within the Integrative Structural Biology theme, but may have natural connectivities to the other current themes. The main beneficiaries will be researchers active in this important area of human health, as well as any evolving technologies or synergies that arise. It is planned that this group will probe important issues that problematic to the field, and also stimulate a wider holistic discussion.