We also looked to cover a wide activity range, spanning from millimolar to nanomolar affinities, and various different fragment optimisation cases, such as the presence of multiple distinct binding sites, changes in net charge, fragment growing and fragment merging (but no fragment linking cases). Note that some cases were specifically avoided to ensure this study remained tractable. For example, large multimeric protein targets were not included to reduce computational costs. Similarly, membrane proteins and systems with binding site metals or known protonation issues were not chosen to avoid introducing additional complexity in this initial dataset. with affinities spanning the millimolar to micromolar range are investigated here.