Fragment-based drug discovery using cryo-EM
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. Harren Jhoti et. al. in Drug Discovery Today review the use of cryo-EM in fragment-based drug discovery (FBDD) based on in-house method development. They 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. In addition, they exemplify this using the test system β-galactosidase (Bgal) and the oncology target pyruvate kinase 2 (PKM2).