Fragment-based drug discovery (FBDD) involves the screening of low-molecular-weight compounds against a target of interest that can be optimized to become larger, more potent lead-like compounds. In collaboration with XChem, I will be exploring how to exploit the rich structural data that result from crystallographic fragment screens to guide fragment-to-lead optimization, primarily using fragment merging approaches. Initial work will focus on improving the efficiency with which we can sample accessible chemical space by identifying fragment merges from commercially available compound libraries, thus overcoming issues with synthetic accessibility. Subsequent work will explore how to prioritize molecules for purchase and/or synthesis and the use of de novo design to generate novel compounds.