EPR Pulsed Dipolar Spectroscopy For Structural Biology

Understanding protein dynamics and conformational flexibility is vital for elucidating disease mechanisms and accelerating drug discovery. Electron paramagnetic resonance (EPR) pulsed dipolar spectroscopy (PDS) provides quantitative distance distributions that measure molecular flexibility, coexisting conformational states, and structural heterogeneity across diverse biological environments. This white paper details how EPR PDS complements established techniques such as Cryo-EM, AlphaFold, NMR, and mass spectrometry by delivering direct, orthogonal restraints for flexible or disordered biomolecular regions.

The publication highlights diverse case studies, including membrane transporter cycles, GPCR signaling, intrinsically disordered proteins, disease-associated mutations, and CRISPR-Cas complexes. Additionally, it introduces the FATHOM automated EPR spectrometer, which features a thin-film superconducting resonator and cryogen-free operation to eliminate traditional barriers of technical complexity and liquid cryogen reliance. Access the full white paper to explore how automated EPR integrates into modern structural biology workflows.