Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method

Restrained and unrestrained aqueous solution molecular dynamics simulations applying the particle mesh Ewald (PME) method to DNA duplex structures pre viously determined via in vacuo restrained molecular dynamics with NMR-deri ved restraints are reported. Without experimental restraints, the DNA decam er, d(CATTTGCATC).d(GATGCAAATG) and trisdecamer, d(AGCTTGCCTTGAG).d(CTCAAGG CAAGCT), structures are stable on the nanosecond time scale and adopt confo rmations in the B-DNA family. These free DNA simulations exhibit behavior c haracteristic of PME simulations previously performed on DNA sequences, inc luding a low helical twist, frequent sugar pucker transitions, B-I-B-II(eps ilon - zeta) transitions and coupled crankshaft (alpha - gamma) motion. Ref inement protocols similar to the original in vacuo restrained molecular dyn amics (RMD) refinements but in aqueous solution using the Cornell et al, fo rce field [Cornell et al. (1995) J. Am. Chem. Sec., 117, 5179-5197] and a p article mesh Ewald treatment produce structures which fit the restraints ve ry well and are very similar to the original in vacuo NMR structure, except for a significant difference in the average helical twist. Figures of meri t fur the average structure found in the RMD PME decamer simulations in sol ution are equivalent to the original in vacuo NMR structure while the figur es of merit for the free MD simulations are significantly higher. The free MD simulations with the PME method, however, lead to some sequence-dependen t structural features in common with the NMR structures, unlike free MD cal culations with earlier force fields and protocols. There is some suggestion that the improved handling of electrostatics by PME improves long-range st ructural aspects which are not well defined by the short-range nature of NM R restraints.