Characterization of internal motions of Escherichia coli ribonuclease H by Monte Carlo simulation

Abstract

The backbone dynamics of Escherichia coli ribonuclease H (RNase H) is studied by a recently developed off-lattice Monte Carlo /Metropolis simulation technique. A low-resolution model (virtual-bond model) is used together with knowledge-based potentials. The calculated mean-square fluctuations in alpha carbons are in good agreement with crystallographic temperature factors. The conformations generated around the native state are analyzed by time-dependent orientational and conformational correlation functions to study the internal motions of RNase at different time windows. A correlation between the free-energy changes for native-state hydrogen exchange (HX) and the extent of the autocorrelation in the rotations of the virtual bonds at long times has been observed. Cross-correlations between the rotations of the bonds, which are near-neighbor in the sequence, are effective in all time windows and help the secondary structures to preserve their kinetic stability. On the other hand, the existence of cross-correlations at long times help the tertiary contacts be maintained. The order parameter of NH bond vector for each residue has been calculated and compared with 15N-NMR relaxation measurements. Proteins 1999;34:533–539. © 1999 Wiley-Liss, Inc.