Measuring dynamic flexibility of the coil state of a helix-forming peptide.

To investigate the dynamic flexibility of the coil state of a helix-forming peptide the end-to-end contact rate was determined. Nanosecond optical excitation of tryptophan at one end of a 22 residue, alanine peptide populates a long-lived triplet state which is quenched upon close contact with a cyclic disulfide attached to the opposite end. Analysis of the decay of the triplet population using a two-state model for helix formation yields the diffusion-limited end-to-end contact rate of the coil state of the peptide as well as the helix-->coil and coil-->helix rates. The helix-coil rates are very similar to those previously measured in laser temperature-jump experiments. The end-to-end contact rate of 1.1 x 10(7) s(-1) in the coil state is tenfold faster than the rate for a disordered peptide with threonine substituted for alanine and, somewhat surprisingly, is about twice the rate for a disordered glycine-containing peptide. These differences are discussed in terms of the theory of Szabo, Schulten and Schulten. The rates should provide important new benchmarks for testing the accuracy of atomistic molecular dynamics simulations.