Oligonucleotide Analogues with a Nucleobase‐Including Backbone,Part 7, Molecular Dynamics Simulation of a DNA Duplex Containing a 2′‐Deoxyadenosine 8‐(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 studied has the sequence 5′‐d(CGTAAGCTCGATAG)‐3′⋅5′‐d(CTATCGA*GCTTACG)‐3′, where the O(3′) of the dG₆ nucleotide in the second strand is linked through a phosphinato group with the O(10) of the dA 2′‐deoxyadenosine‐derived nucleotide. Previous experimental results showed that the stability of this duplex in aqueous solution of 0.1M NaCl at pH 7 and room temperature 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 the experiment, shows that the substitution of the dA nucleotide by the dA* nucleotide in the second strand induces stretching of the double helix, which results in opening of the grooves and consequent exposure of the double‐helix core to the solvent.