Characterization of the residual structure in the unfolded state of the Δ131Δ fragment of staphylococcal nuclease

The determination of the conformational preferences in unfolded states of proteins constitutes an important challenge in structural biology. We use inter-residue distances estimated from site-directed spin-labeling NMR experimental measurements as ensemble-averaged restraints in all-atom molecular dynamics simulations to characterise the residual structure of the Delta131Delta fragment of staphylococcal nuclease under physiological conditions. Our findings indicate that Delta131Delta under these conditions shows a tendency to form transiently hydrophobic clusters similar to those present in the native state of wild-type staphylococcal nuclease. Only rarely, however, all these interactions are simultaneously realized to generate conformations with an overall native topology.