Abstract
The description at atomic level of protein folding is an ambitious goal in biophysics, particularly because of the difficulty in obtaining structural information on unfolded states. Computer simulations can contribute in achieving this goal. Here we report the results of a 10-ns comparative simulation on bovine ribonuclease A and its S-protein, obtained by removal from the native molecule of the first 20 residues, the so-called S-peptide. The atomic trajectories have been analyzed by standard procedures and by applying concepts previously developed for disordered systems. Furthermore, we used a novel approach, described in the preceding paper, to represent graphically the energy landscape of the simulated systems. Relative to RNase-A, the S-protein, while largely maintaining its structural organization, displays an increased structural flexibility, it gains ergodicity and its core loses order, thus indicating that the removal of the S-peptide from ribonuclease A triggers the transition to a folding intermediate with reduced compactness. This finding also has biochemical relevance since the S-protein is recognized as not properly folded by the machinery responsible for the control of the folding quality in the endoplasmic reticulum.