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Nature Chemical Biology 5, 274–275 (1 May 2009) | doi:10.1038/nchembio0509-274

Fragment-based drug discovery takes a virtual turn

Maurizio Pellecchia

Fragment-based drug design (FBDD) is based on the experimental identification of low-molecular-weight core structures (fragments) that initially interact with a target molecule only weakly (usually with dissociation constants in the high micromolar to millimolar range). These initial preferred binding scaffolds are then subjected to modular or stepwise optimization into higher-affinity ligands, much like pieces of a puzzle.