title: The structure of LNA:DNA hybrids from molecular dynamics simulations: the effect of locked nucleotides.
abstract: Locked nucleic acids (LNAs) exhibit a modified sugar fragment that is restrained to the C3'-endo conformation. LNA-containing duplexes are rather stable and have a more rigid structure than DNA duplexes, with a propensity for A-conformation of the double helix. To gain detailed insight into the local structure of LNA-modified DNA oligomers (as a foundation for subsequent exploration of the electron-transfer capabilities of such modified duplexes), we carried out molecular dynamics simulations on a set of LNA:DNA 9-mer duplexes and analyzed the resulting structures in terms of base step parameters and the conformations of the sugar residues. The perturbation introduced by a single locked nucleotide was found to be fairly localized, extending mostly to the first neighboring base pairs; such duplexes featured a B-type helix. With increasing degree of LNA modification the structure gradually changed; the duplex with one complete LNA strand assumed a typical A-DNA structure. The relative populations of the sugar conformations agreed very well with NMR data, lending credibility to the validity of the computational protocol.
authors: Department Chemie, Theoretische Chemie, Technische Universität München, 85747 Garching, Germany.
authors: Anela
authors: A
authors: Ivanova
authors: Notker
authors: N
authors: Rösch
mesh_terms: D001483:Base Sequence; D002236:Carbohydrate Conformation; D003198:Computer Simulation; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000145:classification; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009711:Nucleotides / Q000737:chemistry*
chemical_list: D004277:DNA, Single-Stranded; D009711:Nucleotides