title: NMR structure of a parallel-stranded DNA duplex at atomic resolution.
abstract: DNA dodecamers have been designed with two cytosines on each end and intervening A and T stretches, such that the oligomers have fully complementary A:T base pairs when aligned in the parallel orientation. Spectroscopic (UV, CD and IR), NMR and molecular dynamics studies have shown that oligomers having the sequences d(CCATAATTTACC) and d(CCTATTAAATCC) form a parallel-stranded duplex when dissolved at 1:1 stoichiometry in aqueous solution. This is due to the C:C+ clamps on either end and extensive mismatches in the antiparallel orientation. The structure is stable at neutral and acidic pH. At higher temperatures, the duplex melts into single strands in a highly cooperative fashion. All adenine, cytosine and thymine nucleotides adopt the anti conformation with respect to the glycosidic bond. The A:T base pairs form reverse Watson-Crick base pairs. The duplex shows base stacking and NOEs between the base protons T(H6)/A(H8) and the sugar protons (H1'/H2'/H2") of the preceding nucleotide, as has been observed in antiparallel duplexes. However, no NOEs are observed between base protons H2/H6/H8 of sequential nucleotides, though such NOEs are observed between T(CH3) and A(H8). A three-dimensional structure of the parallel-stranded duplex at atomic resolution has been obtained using molecular dynamics simulations under NMR constraints. The simulated structures have torsional angles very similar to those found in B-DNA duplexes, but the base stacking and helicoid parameters are significantly different.
authors.affiliation: Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
authors.forename: V Rani
authors.initials: VR
authors.lastname: Parvathy
authors.forename: Sukesh R
authors.initials: SR
authors.lastname: Bhaumik
authors.forename: Kandala V R
authors.initials: KV
authors.lastname: Chary
authors.forename: Girjesh
authors.initials: G
authors.lastname: Govil
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
authors.forename: Frank B
authors.initials: FB
authors.lastname: Howard
authors.forename: H Todd
authors.initials: HT
authors.lastname: Miles
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013696:Temperature; D013816:Thermodynamics
chemical_list: D004247:DNA