Water and ion binding around RNA and DNA (C,G) oligomers

The dynamics, hydration, and ion-binding features of two duplexes, the A(r(CG)(12)) and the B(d(CG)(12)), in a neutralizing aqueous environment with 0.25 M added KCl have been investigated by molecular dynamics (MD) simulations. The regular repeats of the same C=G base-pair motif have been exploited as a statistical alternative to long MD simulations in order to extend the sampling of the conformational space. The trajectories demonstrate the larger flexibility of DNA compared to RNA helices. This flexibility results in less well defined hydration patterns around the DNA than around the RNA backbone atoms. Yet, 22 hydration sites are clearly characterized around both nucleic acid structures. With additional results from MD simulations, the following hydration scale for C=G pairs can be deduced: A-DNA < RNA (+3 H2O) and B-DNA < RNA (+2 H2O). The calculated residence times of water molecules in the first hydration shell of the helices range from 0.5 to 1 ns, in good agreement with available experimental data. Such water molecules are essentially found in the vicinity of the phosphate groups and in the DNA minor groove. The calculated number of ions that break into the first hydration shell of the nucleic acids is close to 0.5 per base-pair for both RNA and DNA. These ions form contacts essentially with the oxygen atoms of the phosphate groups and with the guanine N7 and O6 atoms; they display residence times in the deep/major groove approaching 500 ps. Further, a significant sequence-dependent effect on ion binding has been noted. Despite slight structural differences, K+ binds essentially to GpC and not to CpG steps. These results may be of importance for understanding various sequence-dependent binding affinities. Additionally, the data help to rationalize the experimentally observed differences in gel electrophoretic mobility between RNA and DNA as due to the difference in hydration (two water molecules in favor of RNA) rather than to strong ion-binding features, which are largely similar for both nucleic acid structures. (C) 2000 Academic Press.