Expertises
The Biostructural Research unit has set up a pipeline covering everything from cloning of proteins to 3D-structure determination and analysis of protein function. Hence, we are in a position to produce many biologically important target molecules in milligram amounts and of the high purity required for further studies. Target structures provide important information for structure based design of novel compounds and optimization of lead compound. Compounds which are synthesized, tested and optimized in collaboration with medicinal chemistry and synthetic organic chemistry groups.
Cloning and Protein Expression
Subcloning and heterologous expression of proteins in E. coli, Pichia pastoris and insect cells.
Protein Purification and Characterization
Production of pure proteins in mg amounts using standard chromatographic techniques.
Protein characterization, including Isothermal Titration Calorimetry (ITC), Dynamic Light Scattering (DLS) and Dircular Dichroism (CD) spectroscopy.
X-ray Crystallography
Determination of 3D-structures of target molecules, ligand:target complexes,and low-molecular weight compounds, including determination of absolute configuration.
SAXS - Small-angle X-ray Scattering
Ab initio structure determination of target molecules and complexes in solution at lower resolution. Comparison with high-resolution structures and modelling of structural flexibility and conformational changes. Development of high-throughput SAXS in a µTAS.
Molecular Modelling and Computational Chemistry
Computational analysis provides a link between the diversity of experimental data generated by crystallography, in addition to data from medicinal chemists, spectroscopists, pharmacologists, molecular biologists and electrophysiologists. Methods used include homology modelling, force-field based analysis of ligands and binding sites, docking and structure-based design, pharmacophore modelling and database searching, 3D-QSAR, as well as ab initio calculations of small molecule structures, molecular properties and reaction mechanisms in solution.
