Access the Inaccessible with EPR spectroscopy – a powerful tool for probing protein dynamics

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What is Electron Paramagnetic Resonance (EPR) Spectroscopy?

EPR is a biophysical ruler that uses paramagnetic spin labels to measure nanoscale distance distributions within or between biomolecules. The paramagnetic spin labels have no extraneous background signals, making EPR a highly sensitive and unambiguous technique. Additionally, EPR is not limited by size, enabling the study of proteins too large for NMR, and too small for Cryo-EM. EPR is an ensemble technique that measures the breadth of present conformations and provides access to conformational equilibria, dynamics measurements, and intrinsically flexible regions.

 

 

High Q provides next-generation, quantum-enabled EPR solutions for a range of biophysical applications

Ligand-Induced Conformational Changes and GPCRs
G-Protein Coupled Receptors are membrane proteins whose conformational modulations enact diverse cellular functions impacting everything from vision to behavioral regulation. Such broad functionality makes GPCRs the target of over 30% of FDA approved drugs. Precise EPR distance distributions combined with molecular modeling are ideal to assay subtle conformational changes of GPCRs to better understand and target their signaling behavior.
Protein-Protein complexes and Targeted Protein Degradation
Targeted Protein Degraders, such as PROTACs or molecular glues, hijack the cellular waste management system by forming ternary complexes to target and destroy previously undruggable proteins involved in cancers and immune disorders. The efficacy of these methods relies on the fine structure and formation of the ternary complex. Intermolecular EPR distance constraints can shed light on complex formation and quaternary structural arrangements difficult to ascertain via standard biophysical techniques.
Dynamics Measurements and Intrinsically Disordered Proteins
Intrinsically Disordered Proteins break the classic structure-function paradigm for understanding protein activity. Certain IDPs such as amyloid-β and tau protein are responsible for severe neurodegenerative diseases such as Alzheimer’s. While dynamic features are difficult to capture through NMR, Cryo-EM, and X-ray crystallography, EPR reports a probability distribution of distances, inherently sensitive to protein dynamics and flexibility.
Structural Validation and Sample Screening for Cryo-EM and AlphaFold
AlphaFold and Cryo-EM have revolutionized protein structural determination. Microscopy time is valuable – make the most of instrument availability by screening protein structure and conformation with EPR to optimize sample preparation and conditions. EPR distances offer simple, point-to-point constraints for comparison and validation of AlphaFold predictions and Cryo-EM structures.

High Q offers next-generation quantum-enabled EPR spectrometers with comprehensive applications support.

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