To gain additional perspective on the nature of the proposed spine of hydration in DNA, we have carried out (T, V, N) ensemble Monte Carlo-Metropolis computer simulation by using a modified version of the program MMC (16) on a system consisting of d(CGCGAATTCGCG)-d(GCGCTTAAGCGC) in the canonical B-form (17) conformation and 1777 water molecules, a number chosen to provide an excess of two solvation shells for the solute. The calculations were carried out for a hexagonal prism central cell (Fig. 1) under periodic boundary conditions, and thus comprise a representation of a dilute aqueous solution or the aqueous hydration of the dodecamer. The volume of the system was taken to be consistent with an environmental density of 1 gm/ml and the temperature was 298 K. The configurational energies of the system were evaluated under the assumption of pairwise additivity by using atom site potentials, the TIP4P function was developed by Jorgensen et al. (18) for water-water interactions, and TIP4P was spliced with the coulomb and van der Waals terms in the AMBER FF2 force field of Weiner et al. (19) for water-solute interactions. A spherical cutoff at 7.5 A was applied in the evaluation of water-water interaction energies, and solute-water interactions were similar approach to potentials for this system was used earlier in a molecular dynamics simulation on the dodecamer by Seibel et al. (20). Electroneutrality was established by uniformly scaling the nucleic acid charges. This was found to alter any single atomic charge only in the second decimal place, so that the phosphate group remains substantially electronegative, ca. -0.8 atomic units of charge. The simulation was first allowed to proceed for 1,500,000 configurations of equilibration, and the ensemble averages were formed over the next 1,500,000 configurations of the realization. Force bias (21) and preferential sampling (22) were applied to accelerate the Monte Carlo convergence (23). All calculations were carried out on the Cray X-MP/48 supercomputer at the Pittsburgh Supercomputer Center, at a sampling rate of =100,000 configurations per hr. Files were returned locally for display and analysis on an Evans and Sutherland PS-350 color graphics unit by using the comprehensive molecular graphics program "DOCK" (24).
A full description of the aqueous hydration of our model dodecamer is possible from this simulation. Detailed analysis on first-shell solvent coordination, on solute-water pair interaction, and on solute binding energies as well as solvent density distributions, all partitioned by using the proximity criterion (25, 26) into contributions from the major groove, minor groove, and sugar-phosphate backbone of the DNA will be presented elsewhere (P.S.S. and D.L.B., unpublished results). The solvent density plots for the minor groove of the dodecamer have revealed a considerable amount of particular detail relevant to the nature of the spine of hydration and are thus particularly reported and discussed herein. All results are subject to the approximations in our calculations, particularly the choice of canonical B-form for the dodecamer, the assumed intermolecular potential functions, and implicit treatment of counterions.
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