Biophysics

Breaking boundaries with the latest biophysical methodologies

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We deploy state-of-the art biophysical methods to provide exquisite insight on interactions of compounds with biological targets.

Recent advances in biophysical and structural techniques mean that it is now possible to use several label-free approaches to gain crucial insights into ligand-target engagement by understanding the structural basis of drug binding, as well as measuring affinities (dissociation constants), kinetics (kon and koff) and energetics (enthalpic and entropic contributions to drug binding). Domainex is one of the leading experts in generation and interpretation of this data, and we use this knowledge on a routine basis to support both the Hit Identification and Lead Characterisation phases of your drug research projects.

Biophysics
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Biophysical Methodologies

We are able to deploy a suite of high-end technology platforms on your programmes: 

  • NanoTemper thermo-optical instruments, using read-outs based on MicroScale Thermophoresis (MST) and Temperature Related Intensity Change (TRIC) 
  • X-Ray Crystallography
  • Differential Scanning Fluorimetry (DSF)
  • nanoDSF
  • NMR STD & WaterLOGSY
  • Surface Plasmon Resonance (SPR)
  • Isothermal Titration Calorimetry (ITC)

We are adept at deploying these techniques to inform your research project in an efficient and insightful manner. In addition to this, the NanoTemper platform is a much newer technology where Domainex has developed unique know-how that has made us widely recognised as a world-leader in its use.

NanoTemper Thermo-Optical Instruments

State-of-the-art NanoTemper biophysical instruments are at the core of Domainex’s fragment screening platform FragmentBuilder. We also use these instruments for screening and characterising compounds arising from our LeadBuilder virtual screens and subsequently through lead optimisation campaigns. These devices use thermo-optical measurements to quantify the interaction between ligands and biomolecules. Domainex has both the Dianthus NT.23PicoDuo and Monolith NT.Automated high-end instruments in-house.

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Advantages

The advantages of this technology over other biophysical methods include:

  • Target remains in solution and therefore in its native folded state, without the risk of binding sites being occluded by immobilisation
  • Very low protein consumption
  • No molecular weight restrictions on the molecules that can be analysed
  • Eliminates false positives early
  • Minimal assay development time
  • Wide range of buffers can be used
  • Supports challenging biology (e.g. ternary or quaternary systems)
  • Readily allows competitive binding studies to be performed, and orthosteric and allosteric binders to be discovered
  • Binding affinity determinations performed easily, with a large dynamic range (pM–mM)

In our hands MST/TRIC is a very rapid and cost-effective approach to undertaking medium-to-high throughput compound screening. We take great care to perform high-throughput buffer screens to deliver optimized assays in a fast and efficient manner

Our G9a case study is an example of a Fragment Based Drug Design (FBDD) programme where we used our NanoTemper biophysical instruments to specifically identify ligands that were non-competitive with the cofactor S-adenosylmethionine.