WATER-MOLECULES IN DNA RECOGNITION II - A MOLECULAR-DYNAMICS VIEW OF THE STRUCTURE AND HYDRATION OF THE TRP OPERATOR

The structure and hydration of the DNA duplex d-(AGCGT<(ACTAGT)under b ar>ACGCT)(2) corresponding to the trp operator fragment used in the cr ystal structure of the half site complex (PDB entry 1TRR) was studied by a 1.4 ns molecular dynamics simulation in water. The simulation, st arting from a B-DNA conformation, used a non-bonded cutoff of 1.4 nm w ith a reaction field correction and resulted in a stable trajectory. T he average DNA conformation obtained was closer to the ones found in t he crystal structures of the complexes (PDB entries 1TRO and 1TRR) tha n to the crystal structure of unbound trp operator (Nucleic Acid Datab ase entry BDJ061). The DNA hydration was characterized in terms of hyd rogen bond percentages and corresponding residence times. The residenc e times of water molecules within 0.35 nm of the DNA non-exchangeable protons were calculated for comparison with NMR measurements of interm olecular water-DNA NOEs and nuclear magnetic relaxation dispersion mea surements. No significant difference was found between major and minor groove hydration. The DNA donors and accepters were hydrogen bonded t o water molecules for 77(+/-19)% of the time on average. The average r esidence time of the hydrogen bonded water molecules was 11(+/-11) ps with a maximum of 223 ps. When all water molecules within NOE distance (0.35 nm) of non-exchangeable protons were considered, the average re sidence times increased to an average of 100(+/-4) ps and a maximum of 608 ps. These results agree with the experimental NMR results of Sunn erhagen ct al. which did not show any evidence for water molecules bou nd with more than 1 ns residence time on the DNA surface. The exchange of hydration water from the DNA occurred in the major groove primaril y through direct exchange with the bulk solvent, while access to and f rom the minor groove frequently proceeded via pathways involving ribos e O3' and O4' and phosphate O2P oxygen atoms. The most common water di ffusion pathways in the minor groove were perpendicular to the groove direction. In general, water molecules visited only a limited number o f sites in the DNA grooves before exiting. The hydrogen bonding sites, where hydrogen bonds could be formed with donor and acceptor groups o f the DNA, were filled with water molecules with an average B-factor v alue of 0.58 mn(2). No special values were observed at any of the site s, where water molecules were observed both in the trp repressor/opera tor co-crystals and in the crystal structure of unbound DNA. (C) 1998 Academic Press.