title: Hidden complexity in the isomerization dynamics of Holliday junctions.
abstract: A plausible consequence of the rugged folding energy landscapes inherent to biomolecules is that there may be more than one functionally competent folded state. Indeed, molecule-to-molecule variations in the folding dynamics of enzymes and ribozymes have recently been identified in single-molecule experiments, but without systematic quantification or an understanding of their structural origin. Here, using concepts from glass physics and complementary clustering analysis, we provide a quantitative method to analyse single-molecule fluorescence resonance energy transfer (smFRET) data, thereby probing the isomerization dynamics of Holliday junctions, which display such heterogeneous dynamics over a long observation time (T(obs) ≈ 40 s). We show that the ergodicity of Holliday junction dynamics is effectively broken and that their conformational space is partitioned into a folding network of kinetically disconnected clusters. Theory suggests that the persistent heterogeneity of Holliday junction dynamics is a consequence of internal multiloops with varying sizes and flexibilities frozen by Mg(2+) ions. An annealing experiment using Mg(2+) pulses lends support to this idea by explicitly showing that interconversions between trajectories with different patterns can be induced.
authors.affiliation: School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, Korea. hyeoncb@kias.re.kr
authors.forename: Changbong
authors.initials: C
authors.lastname: Hyeon
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Lee
authors.forename: Jeseong
authors.initials: J
authors.lastname: Yoon
authors.forename: Sungchul
authors.initials: S
authors.lastname: Hohng
authors.forename: D
authors.initials: D
authors.lastname: Thirumalai
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D045566:DNA, Cruciform / Q000737:chemistry* / Q000235:genetics; D031541:Fluorescence Resonance Energy Transfer; D007536:Isomerism; D008274:Magnesium / Q000494:pharmacology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D045566:DNA, Cruciform; D008274:Magnesium