Cryo-EM: the resolution revolution and drug discovery
Open accessAbstract
Single-particle cryogenic electron microscopy (cryo-EM) has been elevated to the mainstream of structural biology propelled by technological advancements in numerous fronts, including imaging analysis and the development of direct electron detectors. The drug discovery field has watched with (initial) skepticism and wonder at the progression of the technique and how it revolutionized the molecular understanding of previously intractable targets. This article critically assesses how cryo-EM has impacted drug discovery in diverse therapeutic areas. Targets that have been brought into the realm of structure-based drug design by cryo-EM and are thus reviewed here include membrane proteins like the GABA A receptor, several TRP channels, and G protein-coupled receptors, and multiprotein complexes like the ribosomes, the proteasome, and eIF2B. We will describe these studies highlighting the achievements, challenges, and caveats.
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Recent advances in electron cryo-microscopy and hybrid and integrative methods have accelerated the pace of structure determination.
“Although recent advances in the field of electron cryo-microscopy and hybrid and integrative methods (I/HM) for structure determination have accelerated the pace of structure determination, the gap between known protein sequences and experimental protein structures continues to expand (6,8).”
From AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models (2022) · cites this paper as [8]
The gap between known protein sequences and experimental protein structures continues to expand.
“Although recent advances in the field of electron cryo-microscopy and hybrid and integrative methods (I/HM) for structure determination have accelerated the pace of structure determination, the gap between known protein sequences and experimental protein structures continues to expand (6,8).”
From AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models (2022) · cites this paper as [8]
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- Authors
- de Oliveira, T. M., van Beek, L., Shilliday, F., Debreczeni, J. É., & Phillips, C.
- Affiliations
- AstraZeneca (United Kingdom) (GB)
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- SLAS DISCOVERY
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- Elsevier BV
- Published
- 2021-01
- Volume
- 26
- Issue
- 1
- Pages
- 17-31
- ISSN
- 2472-5552 (ISSN-L)
- OpenAlex
- W3090889851
- Cited by
- 73
- References
- 105
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- 2026: 7 · 2025: 21 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 7 · 2020: 1
- FWCI
- 1.30
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- en
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- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
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- AstraZeneca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- cryo-electron microscopy, drug discovery, structure-based drug design, membrane proteins, GABAA receptor, TRP channels, G protein-coupled receptors, ribosome, proteasome, eIF2B, protein complexes, direct electron detectors
- MeSH terms
- Animals, Humans, Structure-Activity Relationship, Cryoelectron Microscopy, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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