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This lecture covers the principles and applications of Activity-based Protein Profiling (ABPP) for identifying potentially druggable sites on proteins, discussing the advantages and limitations of this approach. It introduces tools like peptide digest, affinity pulldown, and quantitative target ID, showcasing competitive ABPP and gel-based ABPP case studies. The instructor presents strategies for minimizing off-target reactivity of covalent inhibitors and demonstrates the use of ABPP in testing these strategies. In-class exercises involve analyzing data from ABPP experiments to determine the target of covalent binding by probes and evaluate the effectiveness of kinetic-selectivity models.