A 5-NANOSECOND MOLECULAR-DYNAMICS TRAJECTORY FOR B-DNA - ANALYSIS OF STRUCTURE, MOTIONS, AND SOLVATION

We report the results of four new molecular dynamics (MD) simulations on the DNA duplex of sequence d(CGCGAATTCGCG)(2), including explicit c onsideration of solvent water, and a sufficient number of Na+ counteri ons to provide electroneutrality to the system. Our simulations are co nfigured particularly to characterize the latest MD models of DNA, and to provide a basis for examining the sensitivity of MD results to the treatment of boundary conditions, electrostatics, initial placement o f solvent, and run lengths. The trajectories employ the AMBER 4.1 forc e field. The simulations use particle mesh Ewald summation for boundar y conditions, and range in length from 500 ps to 5.0 ns. Analysis of t he results is carried out by means of time series for conformationalm, helicoidal parameters, newly developed indices of DNA axis bending, a nd groove widths. The results support a dynamically stable model of B- DNA for d(CGCGAATTCGCG)(2) over the entire length of the trajectory. T he MD results are compared with corresponding crystallographic and NMR studies on the d(CGCGAATTCGCG)(2) duplex, and placed in the context o f observed behavior of B-DNA by comparisons with the complete crystall ographic data base of B-form structures. The calculated distributions of mobile solvent molecules, both water and counterions, are displayed . The calculated solvent structure of the primary solvation shell is c ompared with the location of ordered solvent positions in the correspo nding crystal structure. The results indicate that ordered solvent pos itions in crystals are roughly twice as structured as bulk water. Deta iled analysis of the solvent dynamics reveals evidence of the incorpor ation of ions in the primary solvation of the minor groove B-form DNA. The idea of localized complexation of otherwise mobile counterions in electronegative pockets in the grooves of DNA helices introduces an a dditional source of sequence-dependent effects on local conformational , helicoidal, and morphological structure, and may have important impl ications for understanding the functional energetics and specificity o f the interactions of DNA and RNA with regulatory proteins, pharmaceut ical agents, and other ligands.