Single-molecule studies of intrinsically disordered proteins

Single-molecule techniques have started to provide important new types of information on the structural and dynamic behavior of intrinsically disordered proteins (IDPs). All single-molecule experiments are by definition able to avoid ensemble averaging since they give information on the smallest possible subensembles of a population. Two of the key strengths of the approaches are their ability to resolve structural and dynamic heterogeneity and to provide quantitative information that can be used for testing physical models. The single-molecule fluorescence approaches available, ranging from Förster Resonance Energy Transfer (FRET) to Positron Emission Topography (PET) and (FCS), can provide information on intra and intermolecular distances and, even more importantly, distance distributions, dynamics on time scales from nanoseconds to seconds, and changes in molecular size or dimensions. Combination of single-molecule fluorescence and ionic current measurements in single-ion channels was developed to monitor structural changes in single channels.