Transnational Call



Screen for ligand-binding by differential scanning fluorimetry (DSF) using purified proteins as targets


UiB is a specialist screening site, integrated together with the Biophysical and Structural Biology facilities in the BiSS Platform ( UiB offers a molecular/biophysical-based screen, monitored by differential scanning fluorimetry (DSF) searching for stabilizer compounds that can be developed into inhibitors or pharmacological chaperones for the correction of misfolding genetic disorders. 

Description of technology offered under this call

The screening site SC-NO University of Bergen (UiB) is a node of the Norwegian screening initiative NOR-OPENSCREEN ( The research group Biorecognition uses a combination of computational and experimental techniques, within the fields of biophysics, biochemistry and cellular biology. UiB has a particular focus on drug discovery for conformational genetic diseases and neurotransmitter disorders and new antibiotics. Collectively, the group has extensive experience with high-throughput screening (HTS) based on differential scanning fluorimetry (DSF) and virtual screening.

DSF constitutes a sensitive assay of ligand binding and an efficient biophysical readout for target-based screening. Customarily, DSF is performed in a real-time PCR instrument with 384- well microplates with the purified target protein sample at concentrations in the range 0.05–0.15 mg/mL in an optimal buffer, and the dye SYPRO Orange that emits fluorescence when interacting with hydrophobic areas of denatured proteins.

The compounds are added to the assay solution to a final concentration of 80 μg/mL and 4% DMSO. Negative DMSO controls are routinely included on each plate. The unfolding curves are then registered from 20 to 95 °C at a 2 °C/min scan rate, and the midpoint melting temperature (Tm) and the corresponding shift relative to the DMSO reference (ΔTm) are calculated for each compound using in-house software. Compounds with significant increases in ΔTm are selected and those showing adequate follow-up concentration-dependent DSF curves are provided as primary stabilizing hits. 

Number of compounds screened

100,000 (full commercial set) of the EU-OPENSCREEN ERIC compound library

Time frame for screen up to validated hits

4 months

Machine/Methods offered under this call

  • Automated sample preparation:
    • Bravo automatic liquid handling platform from Agilent.
    • Additional liquid handling instruments (Mosquito) for volumes in the low microliter range.
    • Multidrop.
  • Specialist compound screening equipment LightCycler 480 for differential scanning fluorimetry (DSF); thermal shift assays.
  • Data analysis.

Services provided under this call

  • Pilot screen using 5,000 compounds from the EU-OS compound library by DSF.
  • Analysis of pilot screen data by concentration-dependent DSF.
  • Full screen with the remaining 95,000 compounds of the EU-OS compound library by DSF.
  • Data analysis and subsequent selection of primary hits by in-house software.
  • Hit picking of primary hits for hit validation by Mosquito®.
  • Hit validation by concentration-dependent DSF and determination of approximate Kd-values.


Please note that this project includes the possibility of re-screening during potential chemical optimization under the medicinal chemistry call starting in 2021 (tentative date).

Prerequisites for applicants

The prerequisite starting point to qualify for access is the availability of a purified protein target (approximately 100 mg for screening of the 100.000 compounds). UiB is not locked to specific target classes or disease areas. The applicant should have characterized the stability of the target, performed buffer screens for selection of optimal buffer, characterization of stability to freezing and thawing and best storage conditions for the protein of interest.

The applicant should have a functional assay that allows validation of hits and discrimination of the stabilizing ligands in possible inhibitors, activators or just stabilizers without effect on the activity of the target.

As specifics of the assay transfer procedure may vary between partner sites, the applicant and the individual sites will agree on the appropriate steps and logistics together.


Partner site


Biorecognition Unit, Department of Biomedicine, Faculty of Medicine, UiB. 

SC-NO University of Bergen

Jonas Lies vei 91 

5009 Bergen, Norway