We investigated the behavior of the conformations of Chymotrypsin Inhibitor (CI2) from the native to the denatured states, obtained in Monte Carlo (MC)/Metropolis simulations, where a low-resolution model is used together with knowledge-based potentials. New conformations starting from the X-ray native structure are generated by random perturbations along with a constraint to increase the radius of gyration. Unfolding is also simulated by unrestrained simulations at a higher temperature. All simulations yield a similar sequence of unfolding events. The preferred pathway starts with loss of native contacts between (N-terminal)-beta(3) and continues with beta(2)-beta(3). The persistence of the contacts between beta(1) and beta(2) at intermediate values of the fraction of native contacts (Q); whereas, highly unfolded conformations with only some helical contacts persisting at low values of Q, are observed. Structure-based analysis of the fluctuations of the unfolded conformations by Gaussian Network Model (GNM) reveals that the termini of the chain-C terminus being more mobile-depict relatively higher flexibility with a native-like hinge near beta(2) that divides the structure into two domains. The fluctuations of the two domains are negatively correlated, with partly folded alpha-helix and a small hydrophobic cluster in the middle of the chain displaying positively correlated fluctuations. The most persistent short-range rotational bond correlations are observed between the residues of alpha-helix, C terminus of the beta(1)-part of the reactive site loop, and around the C terminus of the beta(2). The latter regions also appear as hot spots; i.e. high frequency fluctuating regions, of the structure surviving in unfolded conformations. The results imply that the unfolded CI2 has an intrinsic ability to undergo correlated fluctuations along with some residual native structure specifically induced by its sequence, consisting at the lowest level of a single hinge. (C) 2003 Elsevier Ltd. All rights reserved.