MOLECULAR-DYNAMICS OF ALKYLATED DNA

The effect of methylation of the 04 atom of thymine in two oligonucleotide sequences is investigated by molecular dynamics simulations. Three types of environments are considered including: (i) in vacuo calculation, with a distance-dependent dielectric function and unhydrated counter-ions; (ii) in vacuo calculation, with a distance-dependent dielectric constant and hydrated counter-ions; and (iii) with a 9 angstrom thick explicit water layer and counter-ions. In all environments, the oligonucleotide sequence containing the chemically modified thymine paired with guanine is more stable than the oligonucleotide sequence in which the modified thymine is paired with adenine. The methyl group attached to the O4 atom of thymine is found in a syn configuration with respect to the N3 atom. The best fit between the experimental NMR results and the molecular dynamics simulations is obtained using the environment with hydrated counter-ions.