title: Probing the role of structural water in a duplex oligodeoxyribonucleotide containing a water-mimicking base analog.
abstract: Molecular dynamics simulations were performed on models of the dodecamer DNA double-stranded segment, [d(CGCGAATTCGCG)](2), in which each of the adenine residues, individually or jointly, was replaced by the water-mimicking analog 2'-deoxy-7-(hydroxy-methyl)-7-deazaadenosine (hm(7)c(7)dA) [Rockhill, J.K., Wilson,S.R. and Gumport,R.I. (1996) J. Am. Chem. Soc.,118, 10065-10068]. 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 single individual base. Furthermore, the water molecules near the bases in the singly-substituted oligonucleotides are similarly unaffected. Double substitutions lead to differences in all the aforementioned parameters with respect 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 complexes.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, Champaign, 61801, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kosztin
authors.forename: R I
authors.initials: RI
authors.lastname: Gumport
authors.forename: K
authors.initials: K
authors.lastname: Schulten
mesh_terms: D000241:Adenosine / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004247:DNA / Q000138:chemical synthesis; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry*
chemical_list: D009838:Oligodeoxyribonucleotides; D014867:Water; D004247:DNA; D000241:Adenosine