MOLECULAR-DYNAMICS SIMULATIONS OF TRP APOREPRESSORS AND HOLOREPRESSORS - DOMAIN-STRUCTURE AND LIGAND PROTEIN-INTERACTION

Molecular dynamics simulations of the apo- and hole-forms of the trp-r epressor protein were performed under extensively solvated conditions in order to elucidate their dynamic structures and ligand-protein inte ractions, The root mean square fluctuations calculated from the trajec tories agreed with those calculated from X-ray temperature factors, Di stance, distance fluctuation, and dynamic cross-correlation maps were drawn to provide information on the dynamic structures and communicati ons among the domains, A three-domain format has been proposed for the crystal structure (Zhang et al., Nature 327:591-597, 1987); namely, h elices A-C and F of both subunits make up a central core, and D and E of each subunit forms a DNA binding head, The results of the simulatio ns were mostly consistent with the three-domain format, However, helix F was more flexible and freer than other parts of the central core, T he turn DE, the helix-turn-helix DNA binding motif, was free from inte ractions and correlations with other domains in both forms of the repr essor, A comparison of the simulations of the aporepressor and holo-re pressor showed that tryptophan binding made the DNA-binding helix D mo re flexible but helix F less flexible, Several amino acid residues in contact with the bound tryptophan were identified as making concerted motions with it, Interaction energies between the core-pressor and the amino acid residues of the protein were analyzed; the results were mo stly consistent with the mutational experiments. (C) 1994 Wiley-Liss, Inc.