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  Cryo-EM in drug discovery: Achievements, limitations and prospects.

Renaud, J. P., Chari, A., Ciferri, C., Liu, W., Rémigy, H. W., Stark, H., et al. (2018). Cryo-EM in drug discovery: Achievements, limitations and prospects. Nature Reviews Drug Discovery, 17(7), 471-492. doi:10.1038/nrd.2018.77.

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Renaud, J. P., Author
Chari, A.1, Author           
Ciferri, C., Author
Liu, W., Author
Rémigy, H. W., Author
Stark, H.2, Author           
Wiesmann, C., Author
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1Research Group of Structural Biochemistry and Mechanisms, MPI for Biophysical Chemistry, Max Planck Society, ou_3265855              
2Department of Structural Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_2205645              

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 Abstract: Cryo-electron microscopy (cryo-EM) of non-crystalline single particles is a biophysical technique that can be used to determine the structure of biological macromolecules and assemblies. Historically, its potential for application in drug discovery has been heavily limited by two issues: the minimum size of the structures it can be used to study and the resolution of the images. However, recent technological advances - including the development of direct electron detectors and more effective computational image analysis techniques - are revolutionizing the utility of cryo-EM, leading to a burst of high-resolution structures of large macromolecular assemblies. These advances have raised hopes that single-particle cryo-EM might soon become an important tool for drug discovery, particularly if they could enable structural determination for 'intractable' targets that are still not accessible to X-ray crystallographic analysis. This article describes the recent advances in the field and critically assesses their relevance for drug discovery as well as discussing at what stages of the drug discovery pipeline cryo-EM can be useful today and what to expect in the near future.

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Language(s): eng - English
 Dates: 2018-06-082018-07
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/nrd.2018.77
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Title: Nature Reviews Drug Discovery
Source Genre: Journal
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Pages: - Volume / Issue: 17 (7) Sequence Number: - Start / End Page: 471 - 492 Identifier: -