MOLECULAR-DYNAMICS OF B-DNA INCLUDING WATER AND COUNTERIONS - A 140-PS TRAJECTORY FOR D(CGCGAATTCGCG) BASED ON THE GROMOS FORCE-FIELD

A theoretical study of the dynamical structure of the DNA dodecamer d(CGCGAATTCGCG) based on 140 ps of molecular dynamics simulation including water and counterions is reported. The simulation involved the dodecamer and 1927 water molecules and 22 Na+ counterions treated under periodic boundary conditions in a hexagonal prism elementary cell. The force field for the simulation is GROMOS supplemented with a restraint potential for maintaining Watson-Crick base pairing. Extensive Monte Carlo equilibration of the solvent was necessary to prepare thc system in a suitable state to perform a stable dynamical trajectory. The structure at the termination of the trajectory resides clearly in the B-DNA family, 2.3 angstrom root-mean-square deviation from the corresponding canonical form. The analysis of the simulation reveals good accord with a number of features seen in the X-ray crystal structure of the dodecamer, including local axis deformation near the GC/AT interfaces in the sequence and large propeller twist in thc base pairs. The narrowing of the minor groove in the AT region of thc crystal structure is not observed over the time course of the simulation, but it may be a crystal-packing effect. Thc DNA base pairs show a consistent inclination in the simulation, in accord with the interpretation of results obtained from flow dichroism studies of DNA in solution. A comparison of the calculated dynamical structure with a recently proposed NMR structure of the dodecamer in solution is provided. In an additional simulation carried out without the Watson-Crick restraint function, more pronounced axis deformations and base pair openings are observed. A corresponding in vacuo simulation shows that explicit inclusion of the water molecules is necessary to properly support the major and minor groove structure of the DNA helix.