Structural correspondence between the alpha-helix and the random-flight chain resolves how unfolded proteins can have native-like properties.

Recently, we have proposed that, on average, the structure of the unfolded state of small, mostly alpha-helical proteins may be similar to the native structure (the 'mean-structure' hypothesis). After examining thousands of simulations of both the folded and the unfolded states of five polypeptides in atomistic detail at room temperature, we report here a result that seems at odds with the mean-structure hypothesis. Specifically, the average inter-residue distances in the collapsed unfolded structures agree well with the statistics of the ideal random-flight chain with link length of 3.8 A (the length of one amino acid). A possible resolution of this apparent contradiction is offered by the observation that the inter-residue distances in a typical alpha-helix over short stretches are close to the average distances in an ideal random-flight chain.