Loop formation and translational diffusion of intrinsically disordered proteins.

The conformational flexibility and dynamics of unfolded peptide chains is of major interest in the context of protein folding and protein functioning. The rate with which amino acids at different positions along the peptide chain meet sets an upper speed limit for protein folding. By using single-molecule photo-induced energy transfer spectroscopy, we have systematically measured end-to-end and end-to-internal site contact formation rates for several intrinsically disordered protein fragments (IDPs) (11 to 41 amino acids) and have also determined their hydrodynamic radius using dual-focus fluorescence correlation spectroscopy. For interpreting the measured values, we have developed a Brownian dynamics model (based on bead-rod chain dynamics in a thermal bath including hydrodynamic interactions) which quantitatively reproduces all measured data surprisingly well while requiring only two fit parameters. The model provides a complete picture of the peptides' dynamics and allows us to translate the experimental rates and radii into molecular properties of the peptides: We find a persistence length of l_{P}=5.2±1.9Å, a hydrodynamic radius of a=3.5±0.7Å per amino acid, and that excluded volume effects play an important role in the dynamics of IDPs.