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Crystallographic fragment screening in academic cancer drug discovery

Lookup NU author(s): Dr Mathew Martin, Professor Jane Endicott, Professor Martin NobleORCiD, Dr Natalie TatumORCiD


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© 2023Fragment-based drug discovery (FBDD) has brought several drugs to the clinic, notably to target proteins once considered to be challenging, or even undruggable. Screening in FBDD relies upon observing and/or measuring weak (millimolar-scale) binding events using biophysical techniques or crystallographic fragment screening. This latter structural approach provides no information about binding affinity but can reveal binding mode and atomic detail on protein-fragment interactions to accelerate hit-to-lead development. In recent years, high-throughput platforms have been developed at synchrotron facilities to screen thousands of fragment-soaked crystals. However, using accessible manual techniques it is possible to run informative, smaller-scale screens within an academic lab setting. This chapter describes general protocols for home laboratory-scale fragment screening, from fragment soaking through to structure solution and, where appropriate, signposts to background, protocols or alternatives elsewhere.

Publication metadata

Author(s): Martin MP, Endicott JA, Noble MEM, Tatum NJ

Publication type: Book Chapter

Publication status: Published

Book Title: Methods in Enzymology

Year: 2023

Pages: epub ahead of print

Online publication date: 11/07/2023

Acceptance date: 02/04/2023

Publisher: Academic Press Inc.

Place Published: San Diego


DOI: 10.1016/bs.mie.2023.06.021