An innovative method to study target protein-drug interactions by mass spectrometry.

We report the combination of chemical cross-linking and high-resolution mass spectrometry for analyzing conformational changes in target proteins that are induced by drug binding. With this approach conformational changes in the peroxisome proliferator-activated receptor alpha (PPARalpha) upon binding of low-molecular weight compounds were readily detected, proving that the strategy provides a basis to efficiently characterize target protein-drug interactions.