Researched
Cryo-Electron Microscopy (Cryo-EM)
Direct electron detectors made cryo-electron microscopy atomic-resolution (Chemistry Nobel 2017); it now supplies about 45% of new protein structures.
Open in the interactive tree →Biomolecules are flash-frozen in a thin layer of ice and imaged with electrons, so they can be studied in solution rather than as crystals. In the 2010s a 'resolution revolution' in electron cameras pushed maps below the 2-3 Å needed to place amino acids; Jacques Dubochet, Joachim Frank and Richard Henderson received the 2017 Nobel Prize in Chemistry, and by 2020 maps reached 1.22 Å. In 2025 cryo-EM accounted for 45.3% of the 20,974 structures deposited in the Protein Data Bank, against 53.1% for X-ray crystallography, and 11,692 EM maps were released.
Prerequisites
- X-Rays1895
- Quantum Mechanics1925Electron microscopes work because electrons behave as waves (de Broglie)
- Electron Microscope1931-1933Cryo-EM images frozen molecules with the electron microscope
- First Protein Structure1958Cryo-EM extends the structure determination that began with X-ray crystallography
- Integrated Circuit1958-1959Direct electron detectors, a key trigger of the cryo-EM revolution, are CMOS chips
- CMOS Image Sensor1993Direct electron detectors are CMOS active-pixel sensors.
Unlocks
- AI Protein Structure Prediction2020Cryo-EM now supplies many of the new structures that protein-AI models learn from
- mRNA Technology2020Cryo-EM confirmed the stabilised prefusion spike used as the 2020 vaccine antigen