title: Holliday Junction Thermodynamics and Structure: Coarse-Grained Simulations and Experiments.
abstract: Holliday junctions play a central role in genetic recombination, DNA repair and other cellular processes. We combine simulations and experiments to evaluate the ability of the 3SPN.2 model, a coarse-grained representation designed to mimic B-DNA, to predict the properties of DNA Holliday junctions. The model reproduces many experimentally determined aspects of junction structure and stability, including the temperature dependence of melting on salt concentration, the bias between open and stacked conformations, the relative populations of conformers at high salt concentration, and the inter-duplex angle (IDA) between arms. We also obtain a close correspondence between the junction structure evaluated by all-atom and coarse-grained simulations. We predict that, for salt concentrations at physiological and higher levels, the populations of the stacked conformers are independent of salt concentration, and directly observe proposed tetrahedral intermediate sub-states implicated in conformational transitions. Our findings demonstrate that the 3SPN.2 model captures junction properties that are inaccessible to all-atom studies, opening the possibility to simulate complex aspects of junction behavior.
authors.affiliation: Department of Physics, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Wujie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut 06459, USA.|Molecular Biophysics Program, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Nocka
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut 06459, USA.|Molecular Biophysics Program, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Brianne Z
authors.initials: BZ
authors.lastname: Wiemann
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Hinckley
authors.affiliation: Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut 06459, USA.|Molecular Biophysics Program, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Ishita
authors.initials: I
authors.lastname: Mukerji
authors.affiliation: Department of Physics, Wesleyan University, Middletown, Connecticut 06459, USA.|Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, Connecticut 06459, USA.|Molecular Biophysics Program, Wesleyan University, Middletown, Connecticut 06459, USA.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Starr
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D003198:Computer Simulation; D059371:DNA, B-Form / Q000737:chemistry / Q000235:genetics; D045566:DNA, Cruciform / Q000737:chemistry* / Q000235:genetics; D007700:Kinetics; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013696:Temperature; D013816:Thermodynamics
chemical_list: D059371:DNA, B-Form; D045566:DNA, Cruciform