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.

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Candoxin, a novel toxin purified from the venom of the Malayan krait (Bungarus candidus), is a 66-residue polypeptide containing five disulfide bridges, and is a reversible antagonist of postjunctional nicotinic acetylcholine receptors of the neuromuscular junction. A family of structures were calculated using a combination of distance geometry and simulated annealing with nOe, hydrogen bond and dihedral angle constraints. After refinement 19 structures, which satisfy the experimental constraints, were obtained. A comparison of each of the final structures with the average structure, gives an RMSD of 1.20 Å for backbone atoms. Candoxin has an overall conformation similar to other three-finger toxins with a two-stranded and a three-stranded β-sheets. In spite of the low sequence homology, the tertiary fold of candoxin closely resembles those of erabutoxin b and cobrotoxin, with the exception of the disulfide bridge in the Loop I. Though candoxin lags the most conserved Tyr at the origin of the central loop it posses the most popular 3-dimensional array of residues (W31, R35 and K49), which is reported to be critical for curaremimetic neurotoxicity. The presence of the kink at the tip of the first loop (Loop I) caused by the C6-C11 disulphide bridge, shortens the Loop and hence may isolate this portion of the molecule and prevent its interference with the rest of the molecule, and facilitate specific interaction with receptor/acceptor protein. These observations suggest that candoxin may bind to acetylcholine receptor with lower affinity compared to other neurotoxins and hence could account for its relatively lower toxicity.