The combination of the three main activities creates an optimal environment to address increasingly complex problems with X-ray diffraction.

X-ray crystallography is fundamental to our understanding of matter in chemistry and (molecular) biology. Many properties and interactions of molecules depend on their three-dimensional atomic structure. X-ray crystallography can resolve molecular structures to atomic resolution and is applicable to molecules and assemblies ranging in size from a few to thousands of atoms in organic, organometallic, inorganic and pharmaceutical compounds, to molecules containing 10 to 100 thousand atoms in large bio-molecules and bio-molecular assemblies like viruses and ribosomes. Our research group works along three main lines at the international forefront of structural biology and structural chemistry:

Protein crystallography

Our main focus is to understand molecular recognition and regulation in biomedical processes, such as the arrest of bleeding, infection and immunity. Structural data are critical: they provide detailed insights into the precise molecular interactions responsible for recognition and reveal the (sometimes substantial) structural changes upon complex formation associated with molecular regulation. Insights into these complex and detailed interactions are paramount to understanding the molecular mechanisms underlying the protein interaction networks and bio-complexity and to the development of novel therapeutic compounds.

  • Piet Gros: complement immune system, bacterial outer-membrane proteins.
  • Eric Huizinga: haemostasis, viral proteins.
  • Loes Kroon-Batenburg: amyloids.

Chemical crystallography

We perform state-of-the-art single crystal structure determinations in collaboration with synthetic chemists. Model systems that mimic catalytic sites in proteins or synthetic catalysts to be used in the clean production of desired pharmaceuticals or materials are studied for a detailed understanding of the catalytic process at the molecular level. Similarly, crystal structures of pharmaceuticals are studied to obtain experimental evidence of molecular conformations, intermolecular interactions, absolute configuration, polymorphs and details of solvent inclusions. This information is needed as guidance to develop better pharmaceuticals. Supra-molecular structures of self-organizing molecules through intermolecular interactions are studied as part of research aiming at the development of desired new materials.

National Single Crystal X-ray Facility:

  • Martin Lutz
  • Ton Spek (emeritus)

Crystallographic methods

We develop a data-integration method based on the description of the diffraction process with physical parameters. The goal is 1) to perform accurate integration of weak diffraction data so as to acquire an improved data/parameter ratio and thus more precise and reliable structures of macromolecules and 2) unravel complicated diffraction patterns and the underlying structural characteristics, essential for the understanding of physical properties and phase transitions of materials. Ultimately, all types of (para)crystalline diffraction data can be analyzed, including fibers and powders.

We develop software, as part of the program PLATON (Spek, 2003) that implements general solutions for problems that are encountered as part of the structure determination from diffraction data.

  • Ton Spek (emeritus, structure validation software PLATON)
  • Loes Kroon-Batenburg (diffraction data integration EVAL)

The combination of these three main activities creates an optimal environment to address increasingly complex problems with X-ray diffraction, both in terms of molecular size and of disorder due to inherent dynamics of the molecules and complexes. As such our group forms a renowned center for single-crystal X-ray diffraction in The Netherlands, both with respect to protein crystallography and chemical crystallography in the National Single-Crystal Facility.