Proteome-wide small molecule and metabolite interaction mapping

Thermal stabilization of proteins upon ligand binding provides an efficient means to assess binding of small molecules to proteins. We show here that in combination with quantitative mass spectrometry the approach allows for the systematic survey of protein engagement by cellular metabolites and drugs. The profiling of methotrexate, (S)-crizotinib and 2′3′-cGAMP in intact cells identified the respective cognate targets including the transmembrane receptor STING involved in innate immune signalling.