Probing the role of structural water in a duplex oligodeoxyribonucleotide containing a water-mimicking base analog

Molecular dynamics simulations were performed on models of the dodecamer DN A double-stranded segment, [d(CGCGAATTCGCG)](2), in which each of the adeni ne residues, individually or jointly, was replaced by the water-mimicking a nalog 2'-deoxy-7-(hydroxymethyl)-7-deazaadenosine (hm(7)c(7)dA) [Rockhill,J .K., Wilson,S.R. and Gumport,R.I. (1996) J. Am. Chem. Soc., 118, 10065-1006 8]. The simulations, when compared with those of the dodecamer itself, show that incorporation of the analog affects neither the overall DNA structure nor its hydrogen-bonding and stacking interactions when it replaces a sing le individual base. Furthermore, the water molecules near the bases in the singly-substituted oligonucleotides are similarly unaffected. Double substi tutions lead to differences in all the aforementioned parameters with respe ct to the reference sequence. The results suggest that the analog provides a good mimic of specific 'ordered' water molecules observed in contact with DNA itself and at the interface between protein and DNA in specific comple xes.