J. Srinivasan et al., CONTINUUM SOLVENT STUDIES OF THE STABILITY OF DNA, RNA, AND PHOSPHORAMIDATE - DNA HELICES, Journal of the American Chemical Society, 120(37), 1998, pp. 9401-9409
We apply continuum solvent models to investigate the relative stabilit
y of A- and B-form helices for three DNA sequences, d(CCAACGTTGG)(2),
d(ACCCGCGGGT)(2), and d(CGCGAATTCGCG)(2), a phosphoramidate-modified D
NA duplex, p(CGCGAATTCGCG)(2), in which the O3' atom in deoxyribose is
replaced with NH, and an RNA duplex, r(CCAACGUUGG)(2). Structures wer
e taken as snapshots from multi-nanosecond molecular dynamics simulati
ons computed in a consistent fashion using explicit solvent and with l
ong-range electrostatics accounted for using the particle-mesh Ewald p
rocedure. The electrostatic contribution to solvation energies were co
mputed using both a finite-difference Poisson-Boltzmann (PB) model and
a pairwise generalized Born model; nonelectrostatic contributions wer
e estimated with a surface-area-dependent term. To these solvation fre
e energies were added the mean solute internal energies (determined fr
om a molecular mechanics potential) and estimates of the solute entrop
y (from a harmonic analysis). Consistent with experiment, the relative
energies favor B-form helices for DNA and A-form helices for the NP-m
odified system and for RNA. Salt effects, modeled at the linear or non
linear PB level, favor the A-form helices by modest amounts; for d(ACC
CGCGGGT)(2), salt is nearly able to switch the conformational preferen
ce to ''A''. The results provide a physical interpretation for the ori
gins of the relative stabilities of A- and B-helices and suggest that
similar analyses might be useful in a variety of nucleic acid conforma
tional problems.