Dynamic protein interactions probed by NMR spectroscopy

Dynamic protein–protein interactions are essential for diverse cellular processes but often evade structural characterization due to their transient, heterogeneous, and disordered nature. This review focuses on how nuclear magnetic resonance (NMR) spectroscopy can provide detailed, residue-level insights into these complex interactions. By categorizing dynamic interactions into three distinct yet interconnected classes—(1) interactions with multiple binding interfaces, (2) interactions retaining disorder, and (3) interactions that stabilize or induce disorder—we provide a framework for interpreting diverse interaction modes. Through representative case studies, we highlight the value of NMR in decoding dynamic interactions, where disorder and flexibility persist even in high-affinity complexes.