title: Conformation and dynamics of drug-DNA intercalation.
abstract: Molecular dynamics simulations have been undertaken for a B-form dodecanucleotide duplex in solution with and without an intercalated proflavine molecule between the central C.G base pairs. The introduction of this simple intercalator affects both the conformational features and dynamic properties of the oligonucleotide double helix. Changes are seen in the rms atomic fluctuations and anisotropy of phosphate, sugar and base atoms. The backbone conformation is slightly changed on average and more sugars adopt the C3' endo conformation in the simulation of the complex compared with the simulation of the oligonucleotide alone. Both major and minor grooves becomes wider on average with the addition of the intercalating drug. Flanking A.T base pairs on both sides of the intercalation site have undergone an increase in flexibility, with the base pairs, especially at the 5' side, having the N1...N3 hydrogen bonds being broken.
authors.affiliation: Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: P
authors.initials: P
authors.lastname: Herzyk
authors.forename: S
authors.initials: S
authors.lastname: Neidle
authors.forename: J M
authors.initials: JM
authors.lastname: Goodfellow
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011370:Proflavine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D004247:DNA; D011370:Proflavine