Abstract
Traditional chemical proteomics approaches for screening drug targets usually require the immobilization/modification of the drug molecules to pull down the interacting proteins. The solvent-induced protein precipitation (SIP) approach provides an alternative way to study drug-protein interaction by using complex cell lysate directly without modifying a compound of interest. It relies on the fact that the ligand-bound proteins have higher resistance to solvent-induced precipitation. This chapter describes the protocol for identifying drug-target protein interactions by performing unbiased SIP with total cell lysate using a mass spectrometry-based proteomic strategy.