Oligonucleotide analogues with a nucleobase-including backbone part 7 - Molecular dynamics simulation of a DNA duplex containing a 2 '-deoxyadenosine8-(hydroxymethyl)-derived nucleotide

The structure and stability of a 14-mer DNA duplex containing a nucleotide analog with a hydroxymethyl substituent at the C(8) of 2 ' -deoxyadenosine has been investigated by molecular-dynamics simulation. The DNA duplex stud ied has the sequence 5 ' -d(CGTAAGCTCGCATAG)-3 ' .5 ' -d(CTATCGA*GCTTACG)-3 '. where the O(3 ') of the dG(6) nucleotide in the second strand is linked through a phosphinato group with the O(10) of the dA(7)* 2 ' -deoxyadenosi ne-derived nucleotide. Previous experimental results showed that the stabil ity of this duplex in aqueous solution of 0.1m NaCl at pH 7 and room temper ature is significantly lower than that of the corresponding unmodified DNA duplex. Comparison of molecular-dynamics trajectories of the unmodified and modified B-DNA duplexes in aqueous solution, at similar conditions than th e experiment, shows that the substitution of the dA nucleotide by the dA* n ucleotide in the second strand induces stretching of the double helix, whic h results in opening of the grooves and consequent exposure of the double-h elix core to the solvent.