1. Fragment-based drug discovery using cryo-EM.
- Author
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Saur M, Hartshorn MJ, Dong J, Reeks J, Bunkoczi G, Jhoti H, and Williams PA
- Subjects
- Carrier Proteins chemistry, Carrier Proteins metabolism, High-Throughput Screening Assays, Humans, Membrane Proteins chemistry, Membrane Proteins metabolism, Reproducibility of Results, Thyroid Hormones chemistry, Thyroid Hormones metabolism, beta-Galactosidase chemistry, beta-Galactosidase metabolism, Thyroid Hormone-Binding Proteins, Cryoelectron Microscopy methods, Drug Discovery methods
- Abstract
Recent advances in electron cryo-microscopy (cryo-EM) structure determination have pushed the resolutions obtainable by the method into the range widely considered to be of utility for drug discovery. Here, we review the use of cryo-EM in fragment-based drug discovery (FBDD) based on in-house method development. We demonstrate not only that cryo-EM can reveal details of the molecular interactions between fragments and a protein, but also that the current reproducibility, quality, and throughput are compatible with FBDD. We exemplify this using the test system β-galactosidase (Bgal) and the oncology target pyruvate kinase 2 (PKM2)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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