Molecular dynamics simulation of trp-repressor/operator complex: analysis of hydrogen bond patterns of protein-DNA interaction

Molecular dynamics simulation of Escherichia coli trp-repressor/operator co mplex was performed to elucidate protein-DNA interactions in solution for 8 00 ps on special-purpose computer MD-GRAPE. The Ewald summation method was employed to treat the electrostatic interaction without cutoff. DNA kept st able conformation in comparison with the result of the conventional cutoff method, Thus, the trajectories obtained were used to analyze the protein-DN A interaction and to understand the role of dynamics of water molecules for ming sequence specific recognition interface. The dynamical crosscorrelatio n map showed a significant positive correlation between the helix-turn-heli x DNA-binding motifs and the major grooves of operator DNA. The extensive c ontact surface was stable during the simulation. Most of the contacts consi sted of direct interactions between phosphates of DNA and the protein, but several water-mediated polar contacts were also observed. These water-media ted interactions, which were also seen in the crystal structure (Z. Otwinow ski, et al., Nature, 335 (1998) 321) emerged spontaneously from the randomi zed initial configuration of the solvent. This result suggests the importan ce of the water-mediated interaction in specific recognition of DNA by the trp-repressor. consistent with X-ray structural information. (C) 2000 Elsev ier Science B.V. All rights reserved.