title: Molecular dynamics investigations of DNA triple helical models: unique features of the Watson-Crick duplex.
abstract: We have built computer models of triple helical structures with a third poly(dT) strand Hoogsteen base paired to the major groove of a poly(dA).poly(dT) Watson-Crick (WC) base-paired duplex in the canonical A-DNA as well as B-DNA. For the A-DNA form, the sugar-phosphate backbone of the third strand intertwines and clashes with the poly(dA) strand requiring a radical alteration of the duplex to access the hydrogen bonding sites in the major groove. In contrast, when the duplex was in the canonical B-DNA form, the third strand was readily accommodated in the major groove without perturbing the duplex. The triple helical model, with the duplex in the B-DNA form, was equilibrated for 400ps using molecular dynamics simulations including water molecules and counter-ions. During the entire simulations, the deoxyriboses of the adenine strand oscillate between the S-type and E-type conformations. However, 30% of the sugars of the thymine strands-II & III switch to the N-type conformation early in the simulations but return to the S-type conformation after 200ps. In the equilibrium structure, the WC duplex portion of the triplex is unique and its geometry differs from both the A- or B-DNA. the deoxyriboses of the three strands predominantly exhibit S-type conformation. Besides the sugar pucker, the major groove width and the base-tilt are analogous to B-DNA, while the X-displacement and helical twist resemble A-DNA, giving a unique structure to the triplex and the Watson & Crick and Hoogsteen duplexes.
authors.affiliation: Department of Chemistry, Ohio State University, Columbus 43210.
authors.forename: C Y
authors.initials: CY
authors.lastname: Sekharudu
authors.forename: N
authors.initials: N
authors.lastname: Yathindra
authors.forename: M
authors.initials: M
authors.lastname: Sundaralingam
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D005583:Fourier Analysis; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011071:Poly T / Q000737:chemistry; D011067:Poly dA-dT / Q000737:chemistry; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry
chemical_list: D011089:Polydeoxyribonucleotides; D011687:Purines; D011743:Pyrimidines; C051802:triplex DNA; D011071:Poly T; D011067:Poly dA-dT; D004247:DNA; C030986:pyrimidine