Conformational dynamics of chymotrypsin inhibitor 2 by coarse-grained simulations

A coarse-grained dynamic Monte Carlo (MC) simulation method is used to inve stigate the conformational dynamics of chymotrypsin inhibitor 2 (CI2). Each residue is represented therein by two interaction sites, one at the alpha- carbon and the other on the amino acid side-chain. The energy and geometry parameters extracted from databank structures are used. The calculated rms fluctuations of alpha-carbon atoms are in good agreement with crystallograp hic temperature factors. The two regions of the protein that pack against e ach other to form the main hydrophobic core exhibit negatively correlated f luctuations. The conformational dynamics could efficiently be probed by the time-delayed orientational and conformational correlation functions of the virtual bonds: the active site loop, excluding the active site bond, the t urn region, and the N-terminal of the alpha-helix are relatively more mobil e regions of the structure. A correlation is observed between the hydrogen/ deuterium (H/D) exchange behavior and the long-time orientational and confo rmational autocorrelation function values for CI2. A cooperativity in the r otations of the bonds near in sequence is observed at all time windows, whe reas the cooperative rotations of the bonds far along the sequence appear a t long time windows; these correlations contribute to the stability of the secondary structures and the tertiary structure, respectively. Proteins 199 9;37:454-464. (C) 1999 Wiley-Liss, Inc.