Reassessing random-coil statistics in unfolded proteins.
The Gaussian-distributed random coil has been the dominant model for denatured proteins since the 1950s, and it has long been interpreted to mean that proteins are featureless, statistical coils in 6 M guanidinium chloride. Here, we demonstrate that random-coil statistics are not a unique signature of featureless polymers. The random-coil model does predict the experimentally determined coil dimensions of denatured proteins successfully. Yet, other equally convincing experiments have shown that denatured proteins are biased toward specific conformations, in apparent conflict with the random-coil model. We seek to resolve this paradox by introducing a contrived counterexample in which largely native protein ensembles nevertheless exhibit random-coil characteristics. Specifically, proteins of known structure were used to generate disordered conformers by varying backbone torsion angles at random for approximately 8% of the residues; the remaining approximately 92% of the residues remained fixed in their native conformation. Ensembles of these disordered structures were generated for 33 proteins by using a torsion-angle Monte Carlo algorithm with hard-sphere sterics; bulk statistics were then calculated for each ensemble. Despite this extreme degree of imposed internal structure, these ensembles have end-to-end distances and mean radii of gyration that agree well with random-coil expectations in all but two cases.
T. C. Jenkins Department of Biophysics, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Nicholas C
NC
Fitzkee
George D
GD
Rose
D000818:Animals; D008958:Models, Molecular; D008962:Models, Theoretical; D009010:Monte Carlo Method; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
D011506:Proteins