English: 1A. A small molecule is derivatized for immobilization on a solid support, such as a magnetic bead or affinity column. Protein targets bind to the small molecule and can be identified after elution.

1B. A small molecule is attached to an enrichment handle. The enrichment handle is then used to pull down the small molecule-protein complex. 1C. A small molecule molecule is functionalized with a cross-linking group and an enrichment handle. After a target binds the small molecule, the cross-linking group can be activated, often by light, forming a covalent bond between target and small molecule. The enrichment handle is then used to pull down the small molecule-protein complex.

2. Schematic of an immobilization based proteomics workflow. Immobilized targets are digested and analyzed using LC-MS/MS.