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Biochem Soc Trans. 2019 Feb 28;47(1):281-293. doi: 10.1042/BST20180267. Epub 2019 Jan 15.

Cryo-EM in drug discovery.

Author information

1
UCB Pharma, 216 Bath Road, Slough SL1 3WE, U.K. tom.ceska@ucb.com.
2
GSK, GlaxoSmithKline R&D, Gunnelswood Road, Stevenage SG1 2NY, U.K.
3
Heptares Therapeutics Limited, Steinmetz Building, Granta Park, Great Abington, Cambridge CB21 6DG, U.K.
4
Discovery Sciences, IMED Biotech Unit, AstraZeneca, 310 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, U.K.
5
Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, U.K.

Erratum in

Abstract

The impact of structural biology on drug discovery is well documented, and the workhorse technique for the past 30 years or so has been X-ray crystallography. With the advent of several technological improvements, including direct electron detectors, automation, better microscope vacuums and lenses, phase plates and improvements in computing power enabled by GPUs, it is now possible to record and analyse images of protein structures containing high-resolution information. This review, from a pharmaceutical perspective, highlights some of the most relevant and interesting protein structures for the pharmaceutical industry and shows examples of how ligand-binding sites, membrane proteins, both big and small, pseudo symmetry and complexes are being addressed by this technique.

KEYWORDS:

cryo-EM; drug discovery; pharmaceutical; structural biology

PMID:
30647139
DOI:
10.1042/BST20180267
[Indexed for MEDLINE]

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