Fragment screening is usually performed using biophysical methods or X-Ray crystallography on rule of three (Ro3), diversity-orientated (DOS) or natural product-inspired libraries that sample a large portion of the accessible chemical space. These tend also to be biased towards readily adaptable drug-like leads. However, due to their size, fragments rarely have useful affinity, and the initial screen must be followed by a generally tricky design-make-test-analyse (DMTA) cycles , to progress one or more observed hits to biologically relevant potency. Design strategies are commonly classed as fragment linking, merging, or growing, and are ideally supported by advanced computational approaches such as molecular dynamics or informed "SAR by catalogue" .