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Biophysical Screening and Characterization

Facility part of the DDD platform

The facility can provide in depth information on molecular interactions of relevance for all stages of drug discovery projects. The experimental data can range from fast and simple qualitative analyses demonstrating that two molecules interact, to more extensive quantitative analyses that provide mechanistic, kinetic, thermodynamic and chemodynamic information as well as molecular details of complex structures. Fragment and rational design-based approaches can be supported.

The facility supports drug discovery projects belonging to the Drug Discovery and Development Platform, with the aim to identify, prioritize and guide the optimization of lead compounds. Other projects from academic and external researchers may be supported.

SERVICES

•    Determination of interaction mechanisms, kinetics, affinities for hit/lead target interactions (kon, koff, KD)
•    Screening of compound libraries (e.g. SciLifeLab DDD fragment library) using SPR biosensor technology
•    Protein crystallization and X-ray determination of structures of targets and their complexes with hits/leads or Fab-antigen complexes
•    Ranking and classification of compound series using kinetic and affinity data, structure-kinetic relationship analysis
•    Structure analysis for in silico optimization of hit/lead compounds

The information obtained by combining multiple orthogonal methods facilitates the progression of drug discovery and development projects by, for example:
•    Validation of target functionality and confirmation of reference ligand characteristics
•    Identification, validation and characterization of hits/leads
•    Confirmation of target engagement
•    Identification and rationalization of suitable kinetic profiles of leads
•    Resolution of mode-of-action and complex interaction mechanisms
•    Structural support for optimization of hits and leads

EQUIPMENT

  • Biacore T200 surface plasmon resonance (SPR) biosensor technology.
  • Instruments for high-throughput crystallization such as a Mosquito® Crystal liquid handler and a JANSi UVEX-PS 256 plate hotel.
  • DRX2 SwitchSENSE biosensor technology.
  • Monolith NT.Automated microscale thermophoresis (MST) for intrinsic or labelled fluorescence detection with red-blue detectors.
  • Tycho NT.6 differential scanning fluorimeter for intrinsic fluorescence analysis (nanoDSF).