Dataset Information

Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

ABSTRACT: Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of [Formula: see text] central ions and observe distortions from the tetrad topology in their absence. Force-induced unfolding dynamics is then investigated. We show that the unfolding events in the force-extension curves are concomitant to the loss of coordination between the central ions and the guanines of the G-quadruplex. We found lower ruptures forces for the parallel configuration with respect to the antiparallel one, while the behaviour of the force pattern of the parallel RNA appears similar to the parallel DNA. We anticipate that our results will be essential to interpret the fine structure rupture profiles in stretching assays at high resolution and will shed light on the mechanochemical activity of G-quadruplex-binding machinery.

SUBMITTER: Bergues-Pupo AE

PROVIDER: S-EPMC4551928 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

Bergues-Pupo Ana Elisa AE Arias-Gonzalez J Ricardo JR Morón María Carmen MC Fiasconaro Alessandro A Falo Fernando F

Nucleic acids research 20150713 15

Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of [Formula: see ...[more]

PMID: 26170233

Similar Datasets

Project description:Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using laser optical tweezer experiments have begun to reveal the features of the energy landscape that cannot be easily explored using conventional experiments. Upon application of constant force (f), RNA hairpins undergo cooperative transitions from folded to unfolded states whereas subdomains of ribozymes unravel one at a time. Here, we use a self-organized polymer model and Brownian dynamics simulations to probe mechanical unfolding at constant force and constant-loading rate of four RNA structures of varying complexity. For simple hairpins, such as P5GA, application of constant force or constant loading rate results in bistable cooperative transitions between folded and unfolded states without populating any intermediates. The transition state location (DeltaxFTS) changes dramatically as the loading rate is varied. At loading rates comparable to those used in laser optical tweezer experiments, the hairpin is plastic, with DeltaxFTS being midway between folded and unfolded states; whereas at high loading rates, DeltaxFTS moves close to the folded state, i.e., RNA is brittle. For the 29-nucleotide TAR RNA with the three-nucleotide bulge, unfolding occurs in a nearly two-state manner with an occasional pause in a high free energy metastable state. Forced unfolding of the 55 nucleotides of the Hepatitis IRES domain IIa, which has a distorted L-shaped structure, results in well-populated stable intermediates. The most stable force-stabilized intermediate represents straightening of the L-shaped structure. For these structures, the unfolding pathways can be predicted using the contact map of the native structures. Unfolding of a RNA motif with internal multiloop, namely, the 109-nucleotide prohead RNA that is part of the 29 DNA packaging motor, at constant value of rf occurs with three distinct rips that represent unraveling of the paired helices. The rips represent kinetic barriers to unfolding. Our work shows 1), the response of RNA to force is largely determined by the native structure; and 2), only by probing mechanical unfolding over a wide range of forces can the underlying energy landscape be fully explored.

Dataset Information

Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

Publications

Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets