Cryo-EM
Cryo-EM for Challenging Biological Macromolecules
Cryo-electron microscopy (cryo-EM) enables structural characterization of challenging biological targets and macromolecular complexes that may be difficult to study by X-ray crystallography. It is particularly valuable for large protein complexes, membrane proteins, conformationally heterogeneous systems, and protein–ligand or protein–protein assemblies relevant to drug discovery.
Our cryo-EM workflows integrate protein production and sample optimization, negative-stain screening, grid preparation, data collection, image processing, and structural interpretation. By connecting protein science with structural biology, we help generate fit-for-purpose structural insights to support target characterization, mechanism-of-action studies, and structure-guided drug discovery.
Advantages of Cryo-EM
- Supports Targets Challenging for Crystallography: Enables structure determination of samples unamenable to crystallization (such as proteins with flexible regions, membrane proteins, and large complexes).
- Near-Native State: Sample vitrification maintains the target in a state closer to its native conformation than traditional crystallization.
- Low Sample Consumption: Requires minimal material (approximately 0.1 mg).
- Streamlined Preparation: Eliminates the need for extensive protein engineering to induce crystal lattice packing.
Technical Considerations
Achievable resolution depends on sample size, homogeneity, conformational flexibility, particle orientation, grid quality, and data quality. Cryo-EM is particularly well suited to large proteins, membrane proteins, and macromolecular complexes, although advances in instrumentation, sample preparation, and image processing continue to expand the range of targets that can be studied.
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