Pathway proteomics and chemical proteomics team up in drug discovery

Over the last 5 years, impressive technical advances in mass spectrometry-based analysis of proteins have enabled the parallel analysis of subproteomes and entire proteomes, thus triggering the departure from the traditional single gene-single protein-single target paradigm. Today, immunoaffinity chromatography as well as generic purification methods employing engineered composite affinity tags make streamlined identification of protein complexes as molecular machines possible. In addition, use of stable isotope techniques in protein mass spectrometry allows for the characterization of protein complex composition and posttranslational modifications in an increasingly quantitative fashion. Together, these methodologies allow the elucidation of medically relevant biological pathways, and the study of the interaction of their protein components with therapeutic agents, on a much larger scale. The present review discusses some of the current experimental strategies, with a focus on applications in neurobiology.