DNA structure: What's in charge?

DNA structure is well known to be sensitive to hydration and ionic strength . Recent theoretical predictions and experimental observations have raised the idea of the intrusion of monovalent cations into the minor groove spine of hydration in B-form DNA. To investigate this further, extensions and fu rther analysis of molecular dynamics (MD) simulations on d(CGCCGAATTCGCG), d(ATAGGCAAAAAATAGG-CAAAAATGG) and d(G(5)-(GA(4)T(4)C)(2)-C-5), including co unterions and water, have been performed. To examine the effective of minor groove ions on structure, we analyzed the MD snapshots from a 15 ns trajec tory on d(CGCGAATTCGCC) as two subsets: those exhibiting a minor groove wat er spine and those with groove-bound ions. The results indicate that Na+ at the ApT step of the minor groove of d(CGCCGAATTCGCG) makes only small loca l changes in the DNA structure, and these changes are well within the therm al fluctuations calculated from the MD. To examine the effect of ions on th e differential stability of a B-form helix, further analysis was performed on two Longer oligonucleotides, which exhibit A-tract-induced axis bending localized around the CpG step in the major groove. Plots of axis bending an d proximity of ions to the bending locus were generated as a function of ti me and revealed a strong linear correlation, supporting the idea that mobil e cations play a key role in local helix deformations of DNA and indicating ion proximity just precedes the bending event. To address the issue of "wh at's in charge?" of DNA structure more generally, the relative free energy of A and B-form d(CGCCAATTCGCC) structures from MD simulations under variou s environmental circumstances were estimated using the free energy componen t method. The results indicate that the dominant effects on conformational stability come from the electrostatic free energy, but not exclusively from groove bound ions per sc, but from a balance of competing factors in the e lectrostatic free energy, including phosphate repulsions internal to the DN A, the electrostatic component of hydration (i.e. solvent polarization), an d electrostatic effects of the counterion atmosphere. In summary, free ener gy calculations indicate that the electrostatic component is dominant, MD s hows temporal proximity of mobile counterions to be correlated with A-track -induced bending, and thus the mobile ion component of electrostatics is a significant contributor. However, the MD structure of the dodecamer d(CGCGA ATTCGCG) is not highly sensitive to whether there is a sodium ion in the mi nor groove. (C) 2000 Academic Press.