Methylene blue binding to DNA with alternating GC base sequence: Continuumtreatment of salt effects

Methylene blue (MB), an efficient singlet oxygen generating photoactive dye , binds to DNA and allows photosensitized reactions to be used for sequence -specific cleavage of the DNA backbone. Intercalation and groove binding ar e possible binding modes of the dye, depending on base sequences and enviro nmental conditions. In a recent modeling study of methylene blue binding to a double stranded DNA decamer with an alternating GC sequence, six structu ral models for intercalation structures and for minor and major groove bind ing have been obtained. By estimating the binding energies (including elect rostatic reaction field contributions of a salt-free aqueous solvent), symm etric intercalation at the 5'-CpG-3' and 5'-GpC-3' steps was found as the p redominant binding mode, followed by a slightly weaker binding of the dye i n the minor groove. In this study, the stability of the modeled structures has been analysed as a function of salt concentration. The results of finit e difference numerical solutions of the non-linear Poisson-Boltzmann equati on show that the stabilizing effect of salt is larger for free DNA than for the modeled MB-DNA complexes. Accordingly, the estimated binding energies decrease with increasing ionic strength. A slightly higher stabilization of the groove binding complexes results in comparable binding energies for sy mmetric intercalation and minor groove binding at high salt concentration. Both results are in qualitative agreement with experimental data.