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Cryo-EM for structural analysis of protein complexes
Despite their power, classical biochemical methods provide only low-resolution or indirect constraints on macromolecular architecture. They report on mass, oligomeric state, surface accessibility, or conformational perturbations, but not the full three-dimensional arrangement of domains, cofactors, and interaction interfaces. As a result, many mechanistic questions remain underdetermined, even after exhaustive protein analysis.
By allowing direct imaging of proteins in native-like states, cryo-electron microscopy (cryo-EM) provides biochemists with more detailed and accurate insights into protein analysis. Cryo-EM overcomes the structural ambiguity inherent to traditional workflows by delivering near-atomic reconstructions of proteins and complexes in multiple functional states, enabling precise mapping of biochemical observations onto real molecular models. For researchers aiming to unify activity, dynamics, and structure, cryo-EM has become the bridge between biochemical characterization and mechanistic insight.
Single particle analysis for high-resolution protein structure determination
Single particle analysis is a cryo-EM technique performed using a cryo-transmission electron microscopy (cryo-TEM) to image thousands to millions of individual protein particles that are randomly oriented and cryogenically preserved in conditions close to their native environment. Advanced detectors and software identify, align, and average these particles to reconstruct high-resolution, three-dimensional structures. This approach is one type of protein microscopy, allowing researchers to visualize proteins without the need for crystallization, labeling, or extensive sample modification.
The benefits for protein analysis are significant: single particle analysis enables the study of proteins that are difficult or impossible to crystallize, captures multiple conformational states in a single experiment, and reveals subtle structural differences linked to function or disease.
Cryo-EM of large protein complexes, membrane proteins, and flexible signaling complexes
Structural protein analysis in rational drug design
Single particle analysis provides high-resolution structural insight into protein targets in conditions that closely reflect their native biological environment. Acting as a powerful protein microscope, cryo-TEMs enables researchers to visualize binding pockets, conformational changes, and protein–ligand interactions with exceptional clarity. By revealing multiple functional states of a target in a single experiment, single particle analysis supports structure-guided drug design, improves hit-to-lead optimization, and reduces uncertainty early in development. The result is a faster, more informed pathway to designing therapeutics with improved specificity, efficacy, and safety.
Start or scale your cryo-EM facility for protein structure research
Cryo-TEM platforms for protein microscopy are engineered at 100, 200, and 300 kV to support distinct levels of protein analysis, providing a range of solutions tailored to different protein research challenges.
100 kV cryo-TEMs, such as the Thermo Scientific Tundra Cryo-TEM, provide accessibility for screening, sample optimization, and routine protein analysis, making them ideal for rapid assessment and method development.
200 kV systems, such as the Thermo Scientific Glacios 3 Cryo-TEM, strike a balance between accessibility and resolution, supporting high-quality cryo-EM while offering efficient throughput and flexibility.
Pictured above are Thermo Scientific Tundra Cryo-TEM (left), Glacios 3 Cryo-TEM (middle), Krios 5 Cryo-TEM (right)
300 kV cryo-TEMs, such as the Thermo Scientific Krios 5 Cryo-TEM, deliver the highest resolution and deepest penetration, enabling atomic-level structural determination of large, complex, or thick specimens and supporting the most demanding protein analysis and drug discovery applications.
Together, these cryo-TEM platforms offer protein microscopy that support discovery from early screening through high-resolution structural insight.
Resources for your journey into electron microscopy of proteins
eBooks
For Research Use Only. Not for use in diagnostic procedures.