title: Spectroscopic and molecular dynamics evidence for a sequential mechanism for the A-to-B transition in DNA.
abstract: The A-to-B form transition has been examined in three DNA duplexes, d(CGCGAATTCGCG)(2), d(CGCGAATTGCGC), and d(CGCAAATTTCGC), using circular dichroism spectroscopy, ultraviolet resonance Raman (UVRR) spectroscopy, and molecular dynamics (MD) simulation. Circular dichroism spectra confirm that these molecules adopt the A form under conditions of reduced water activity. UVRR results, obtained under similar conditions, suggest that the transition involves a series of intermediate forms between A and B. Cooperative and distinct transitions were observed for the bases and the sugars. Independent MD simulations on d(CGCGAATTCGCG)(2) show a spontaneous change from the A to B form in aqueous solution and describe a kinetic model that agrees well with UVRR results. Based on these observations, we predict that the mechanism of the transition involves a series of A/B hybrid forms and is sequential in nature, similar to previous crystallographic studies of derivatized duplexes. A simulation in which waters were restrained in the major groove of B DNA shows a rapid, spontaneous change from B to A at reduced water activity. These results indicate that a quasiergodic sampling of the solvent distribution may be a problem in going from B to A at reduced water activity in the course of an MD simulation.
authors.affiliation: Molecular Biology and Biochemistry Department, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Knee
authors.forename: Surjit B
authors.initials: SB
authors.lastname: Dixit
authors.forename: Colin Echeverría
authors.initials: CE
authors.lastname: Aitken
authors.forename: Sergei
authors.initials: S
authors.lastname: Ponomarev
authors.forename: D L
authors.initials: DL
authors.lastname: Beveridge
authors.forename: Ishita
authors.initials: I
authors.lastname: Mukerji
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure*; D044704:DNA, A-Form / Q000737:chemistry / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D044367:Phase Transition; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D044704:DNA, A-Form; D004247:DNA