Probing small molecule-protein interactions: A new perspective for functional proteomics

► Modular chemical probes enable the isolation of subproteomes defined by functional small molecule-protein interactions. ► Leading strategies are Activity-based protein profiling, affinity pulldown, and Capture Compound mass spectrometry. ► Profiling small molecule-protein interactions contributes to the functional annotation of genomes. ► The approaches enable unbiased direct proteomic screens to identify all proteins that interact with a given drug molecule.