Chemical cross-linking and high-resolution mass spectrometry to study protein-drug interactions.

This method describes the combination of chemical cross-linking and high-resolution mass spectrometry for analyzing conformational changes in target proteins that are induced by drug binding. Our approach is exemplified for detecting conformational changes within the peroxisome proliferator-activated receptor alpha upon binding of low-molecular weight compounds, proving that our strategy provides a basis to efficiently characterize target protein-drug interactions.