Molecular dynamics studies of the conformational preferences of a DNA double helix in water and an ethanol/water mixture:: Theoretical considerations of the A↔B transition

A series of molecular dynamics (MD) computer simulations were carried out to explore the conformational preferences of a dynamic model of the sodium salt of the DNA duplex d(CGCGAATTCGCG) in water and in a mixed solvent comprised of 85% (v/v) ethanol/water. This sequence is observed to assume a B-form structure in the solid state and in aqueous solution and is expected to assume an A-form structure in the mixed solvent environment. The MD simulations are based on the empirical force field proposed recently by Cornell et al.(1) and carried out with long-range interactions treated via the particle mesh Ewald method using the AMBER 4.1 modeling package.(2-4) This study builds on the results of a previous 5 ns MD simulation on d(CGCGAATTCGCG) in water,(5) now extended to 13 ns, which resulted in a well-stabilized B-form dynamical structure. Three additional simulations are reported: one simulation starts from the A-form in water, the second starts from the A-form in 85% (v/v) ethanol/water, the last starts from the B-forms in 85% (v/v) ethanol/water. The MD on the A-form structure in water undergoes an A-to B-DNA transition and stabilizes in the B-form. The corresponding 2.0 ns MD in ethanol/water remains an A-form structure, as expected. However, the B-form structure in the 85% (v/v) ethanol/water remains B-form even after 2.0 ns of MD, contrary to expectation. Comparisons of our results with those of parallel studies based on AMBER and pertinent results obtained using other current force fields are provided, and the use of conformational preferences as a performance index for nucleic acids force fields is discussed.