Politis Lab published a new Perspective in Chemical Science to examine how hydrogen/deuterium exchange mass spectrometry (HDX-MS) can be used to probe the structural dynamics of membrane proteins and their interactions with the lipid environment. Building on recent advances in HDX-MS, Drs Lioupi, Gavriilidou and Politis discuss key challenges associated with lipid-induced ion suppression and chromatographic interference, while also describing emerging strategies to overcome these limitations. The authors further discuss complementary approaches, including lipidomics, native mass spectrometry, molecular dynamics simulations, and artificial intelligence, that can be combined with HDX-MS to provide a more comprehensive understanding of protein–lipid interactions.

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