Fragment-Based Ligand Discovery

Ben J. Davis, Roderick E. Hubbard

Research output: Chapter in Book/Report/Conference proceedingChapter


The methods of fragment-based lead discovery (FBLD) have matured considerably and are an accepted part of the armory of techniques used to identify initial hit compounds for initiating either a chemical biology or drug discovery project. This chapter reviews the evolution of the methods and summarizes the essential features of a fragment-based discovery platform, illustrated with some recent success stories. It presents some extended discussion of some of the practical aspects of fragments based on the author's experiences and the literature. A fragment-based discovery campaign has three main components - a library of fragments, a method for identifying which fragments bind to the target (screening), and a strategy for evolving the fragments to hits that register in conventional assays. One key point is that as many orthogonal techniques should be applied, and their output interpreted skeptically, to identify an optimal set of validated fragment hits.

Original languageEnglish
Title of host publicationStructural Biology in Drug Discovery
Subtitle of host publicationMethods, Techniques, and Practices
EditorsJean-Paul Renaud
Number of pages20
ISBN (Electronic)9781118681121
ISBN (Print)9781118900406
Publication statusPublished - 1 Jan 2020

Bibliographical note

Publisher Copyright:
© 2020 John Wiley & Sons, Inc. All rights reserved.


  • fragment evolution
  • fragment hits
  • fragment libraries
  • fragment screening
  • fragment-based ligand discovery

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