Proteins are molecular machines with a well-defined 3D structure, and it is mainly the success of X-ray and NMR spectroscopic techniques that made the tremendous progress in structural biology happen. However, it is also clear that biomolecular processes generally involve conformational changes of proteins and enzymes. Mostly due to a lack of appropriate spectroscopic tools, much less is known about the dynamics of protein structures.
Protein dynamics occurs on a large range of time scales, which can coarsely be related to various length scales: Dynamics of tertiary and quaternary structure extends from milliseconds to seconds and even longer, while formation of secondary structure has been observed between 50 ns and a few microseconds [1–12]. Nevertheless, several experiments have provided strong hints for the relevance of even faster processes from the observation of large instantaneous signals, which could not be time-resolved [2, 7, 13]. For example, Thompson et al.  estimated a “zipping time” for a 21-residue α-helix of 300 ps (i.e., the time for closing of subsequent hydrogen bonds, once an initial helix turn is formed), while Huang et al.  indirectly concluded that helix nucleation might occur on a subnanosecond time scale. Also molecular dynamics (MD) simulations suggest that peptides and proteins can undergo considerable structural changes within 1 ns or less [8–10, 14, 15]. Hummer et al.  found the formation of the first α-helical turn within 0.1–1 ns in work on helix nucleation in short Ala and Gly based peptides. Daura et al. [9, 17] simulated equilibrium folding/unfolding of a β-heptapeptide at the melting point and above to obtain statistics on the populations of the folded and unfolded states. Several folding/unfolding events were observed in a 50 ns trajectory, where the actual transitions from unfolded to folded conformations could be as fast as 50–100ps.