Chapter 8: Structural Insight into the Slowly Exchanging Dark States at the Functional Interaction Interface

Protein dynamics at biomolecular binding interfaces yield essential functional information. However, owing to their transient nature and relatively high–molecular–weight, these dynamic conformers have remained invisible or dark to spectroscopic intervention. Recent advances in solution-state NMR has enabled the development of Dark State Exchange Saturation Transfer (DEST) experiments to gain atomic-resolution insight into these “dark” conformers through radio-frequency saturation. DEST is particularly efficient at probing slow biomolecular chemical exchange, which provides invaluable information on the dynamic aspect of the interactions.