Perspective: Chain dynamics of unfolded and intrinsically disordered proteins from nanosecond fluorescence correlation spectroscopy combined with single-molecule FRET

The dynamics of unfolded proteins are important both for the process of protein folding and for the behavior of intrinsically disordered proteins. However, methods for investigating the global chain dynamics of these structurally diverse systems have been limited. A versatile experimental approach is single-molecule spectroscopy in combination with Förster resonance energy transfer and nanosecond fluorescence correlation spectroscopy. The concepts of polymer physics offer a powerful framework both for interpreting the results and for understanding and classifying the properties of unfolded and intrinsically disordered proteins. This information on long-range chain dynamics can be complemented with spectroscopic techniques that probe different length scales and time scales, and integration of these results greatly benefits from recent advances in molecular simulations. This increasing convergence between the experiment, theory, and simulation is thus starting to enable an increasingly detailed view of the dynamics of disordered proteins.