Size, shape, and flexibility of RNA structures

Determination of sizes and flexibilities of RNA molecules is important in understanding the nature of packing in folded structures and in elucidating interactions between RNA and DNA or proteins. Using the coordinates of the structures of RNA in the Protein Data Bank we find that the size of the folded RNA structures, measured using the radius of gyration, $R_G$, follows the Flory scaling law, namely, $R_G =5.5 N^{1/3}$ \AA where N is the number of nucleotides. The shape of RNA molecules is characterized by the asphericity $\Delta$ and the shape $S$ parameters that are computed using the eigenvalues of the moment of inertia tensor. From the distribution of $\Delta$, we find that a large fraction of folded RNA structures are aspherical and the distribution of $S$ values shows that RNA molecules are prolate ($S>0$). The flexibility of folded structures is characterized by the persistence length $l_p$. By fitting the distance distribution function $P(r)$ to the worm-like chain model we extracted the persistence length $l_p$. We find that $l_p\approx 1.5 N^{0.33}$ \AA. The dependence of $l_p$ on $N$ implies the average length of helices should increases as the size of RNA grows. We also analyze packing in the structures of ribosomes (30S, 50S, and 70S) in terms of $R_G$, $\Delta$, $S$, and $l_p$. The 70S and the 50S subunits are more spherical compared to most RNA molecules. The globularity in 50S is due to the presence of an unusually large number (compared to 30S subunit) of small helices that are stitched together by bulges and loops. Comparison of the shapes of the intact 70S ribosome and the constituent particles suggests that folding of the individual molecules might occur prior to assembly.Comment: 28 pages, 8 figures, J. Chem. Phys. in pres

Stretching of a single-stranded DNA: Evidence for structural transition

Recent experiments have shown that the force-extension (F-x) curve for single-stranded DNA (ssDNA) consisting only of adenine [poly(dA)] is significantly different from thymine [poly(dT)]. Here, we show that the base stacking interaction is not sufficient to describe the F-x curves as seen in the experiments. A reduction in the reaction co-ordinate arising from the formation of helix at low forces and an increase in the distance between consecutive phosphates of unstacked bases in the stretched state at high force in the proposed model, qualitatively reproduces the experimentally observed features. The multi-step plateau in the F-x curve is a signature of structural change in ssDNA.Comment: 10 pages, 4 figure

Stretching an heteropolymer

We study the influence of some quenched disorder in the sequence of monomers on the entropic elasticity of long polymeric chains. Starting from the Kratky-Porod model, we show numerically that some randomness in the favoured angles between successive segments induces a change in the elongation versus force characteristics, and this change can be well described by a simple renormalisation of the elastic constant. The effective coupling constant is computed by an analytic study of the low force regime.Comment: Latex, 7 pages, 3 postscript figur

Structural, mechanical and thermodynamic properties of a coarse-grained DNA model

We explore in detail the structural, mechanical and thermodynamic properties of a coarse-grained model of DNA similar to that introduced in Thomas E. Ouldridge, Ard A. Louis, Jonathan P.K. Doye, Phys. Rev. Lett. 104 178101 (2010). Effective interactions are used to represent chain connectivity, excluded volume, base stacking and hydrogen bonding, naturally reproducing a range of DNA behaviour. We quantify the relation to experiment of the thermodynamics of single-stranded stacking, duplex hybridization and hairpin formation, as well as structural properties such as the persistence length of single strands and duplexes, and the torsional and stretching stiffness of double helices. We also explore the model's representation of more complex motifs involving dangling ends, bulged bases and internal loops, and the effect of stacking and fraying on the thermodynamics of the duplex formation transition.Comment: 25 pages, 16 figure

The Yamabe invariant for axially symmetric two Kerr black holes initial data

An explicit 3-dimensional Riemannian metric is constructed which can be interpreted as the (conformal) sum of two Kerr black holes with aligned angular momentum. When the separation distance between them is large we prove that this metric has positive Ricci scalar and hence positive Yamabe invariant. This metric can be used to construct axially symmetric initial data for two Kerr black holes with large angular momentum.Comment: 14 pages, 2 figure

Uniqueness and Non-uniqueness in the Einstein Constraints

The conformal thin sandwich (CTS) equations are a set of four of the Einstein equations, which generalize the Laplace-Poisson equation of Newton's theory. We examine numerically solutions of the CTS equations describing perturbed Minkowski space, and find only one solution. However, we find {\em two} distinct solutions, one even containing a black hole, when the lapse is determined by a fifth elliptic equation through specification of the mean curvature. While the relationship of the two systems and their solutions is a fundamental property of general relativity, this fairly simple example of an elliptic system with non-unique solutions is also of broader interest.Comment: 4 pages, 4 figures; abstract and introduction rewritte

Perturbative Solutions of the Extended Constraint Equations in General Relativity

The extended constraint equations arise as a special case of the conformal constraint equations that are satisfied by an initial data hypersurface $Z$ in an asymptotically simple spacetime satisfying the vacuum conformal Einstein equations developed by H. Friedrich. The extended constraint equations consist of a quasi-linear system of partial differential equations for the induced metric, the second fundamental form and two other tensorial quantities defined on $Z$, and are equivalent to the usual constraint equations that $Z$ satisfies as a spacelike hypersurface in a spacetime satisfying Einstein's vacuum equation. This article develops a method for finding perturbative, asymptotically flat solutions of the extended constraint equations in a neighbourhood of the flat solution on Euclidean space. This method is fundamentally different from the `classical' method of Lichnerowicz and York that is used to solve the usual constraint equations.Comment: This third and final version has been accepted for publication in Communications in Mathematical Physic

A new geometric invariant on initial data for Einstein equations

For a given asymptotically flat initial data set for Einstein equations a new geometric invariant is constructed. This invariant measure the departure of the data set from the stationary regime, it vanishes if and only if the data is stationary. In vacuum, it can be interpreted as a measure of the total amount of radiation contained in the data.Comment: 5 pages. Important corrections regarding the generalization to the non-time symmetric cas

High-throughput alternative splicing quantification by primer extension and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Alternative splicing is a significant contributor to transcriptome diversity, and a high-throughput experimental method to quantitatively assess predictions from expressed sequence tag and microarray analyses may help to answer questions about the extent and functional significance of these variants. Here, we describe a method for high-throughput analysis of known or suspected alternative splicing variants (ASVs) using PCR, primer extension and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Reverse-transcribed mRNA is PCR amplified with primers surrounding the site of alternative splicing, followed by a primer extension reaction designed to target sequence disparities between two or more variants. These primer extension products are assayed on a MALDI-TOF mass spectrometer and analyzed automatically. This method is high-throughput, highly accurate and reproducible, allowing for the verification of the existence of splicing variants in a variety of samples. An example given also demonstrates how this method can eliminate potential pitfalls from ordinary gel electrophoretic analysis of splicing variants where heteroduplexes formed from different variants can produce erroneous results. The new method can be used to create alternative variant profiles for cancer markers, to study complex splicing regulation, or to screen potential splicing therapies