The potential of cross-linking mass spectrometry in the development of protein–protein interaction modulators

Cross-linking mass spectrometry (XL-MS) can provide a wealth of information on endogenous protein–protein interaction (PPI) networks and protein binding interfaces. These features make XL-MS an attractive tool to support the development of PPI-targeting drugs. Though not yet widely used, applications of XL-MS to drug characterization are beginning to emerge. Here, we compare XL-MS to established structural proteomics methods in drug research, discuss the current state and remaining challenges of XL-MS technology, and provide a perspective on the future role XL-MS can play in drug development, with a particular emphasis on PPI modulators.