SARomics Biostructures' structural biology and drug discovery platform offers the following services:
The platform is built up to include all major techniques required for successful protein structure determination and structure-based drug design. Following cloning, expression and purification of a protein (gene-to-structure services), and before the start of an X-ray crystallography or NMR spectroscopy project, we perform a thorough biophysical characterization of the protein in solution. Both for successful crystallization and for NMR studies we need monodisperse protein solutions, which do not contain any aggregated or denatured material. The protein also needs to be stable within a certain range of pH, ionic strength and temperature since these values will be varied in the crystallization screens. It should always be kept in mind that a proper characterization of the protein solution is crucial for the success of a structure determination project!
For protein characterisation we use a number of biophysical techniques which include:
• NMR spectroscopy
• Dynamic light scattering (DLS)
• CD spectroscopy
• Differential scanning fluorimetry (DSF, similar to thermal-shift assay)
After crystallization, high resolution X-ray diffraction data are collected at MAX IV synchrotron radiation facility in Lund or at one of the European synchrotrons like Diamond Light Source, European Synchrotron Radiation Facility (ESRF), Swiss Light Source (SLS), etc. Generally we collect X-ray data on average every 2 to 3 weeks.
More details on our technology plattform may be found on the respective pages:
• Crystallization and crystallography
• Protein NMR spectroscopy
Human dihydroorotate dehydrogenase, PDB ID 2WV8
Carbohydrate-Binding Module from Thermostable Rhodothermus marinus Xylanase, PDB ID 2Y64
Death associated protein kinase-3 (DAPK3), 5A6N
SPBc2 prophage derived protein YomS, PDB ID 6I5O
Omega transaminase from Chromobacterium violaceum, PDB ID 6S4G
Our structure-based drug discovery services plattform is built up around our proprietary weak affinity chromatography technology (WAC™), which is used for screening compound libraries and hit identification. Next step in the process is hit expansion and generation of lead compounds. This part involves both medicinal chemistry and extensive X-ray crystallographic studies of the complexes of generated ligands with the target protein.
Depending on the information available, different drug discovery strategies can be followed. Availability of three-dimensional structural information will always substantially accelerate the process.