Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots

The Kinefold web server provides a web interface for stochastic folding simulations of nucleic acids on second to minute molecular time scales. Renaturation or co-transcriptional folding paths are simulated at the level of helix formation and dissociation in agreement with the seminal experimental results. Pseudoknots and topologically ‘entangled’ helices (i.e. knots) are efficiently predicted taking into account simple geometrical and topological constraints. To encourage interactivity, simulations launched as immediate jobs are automatically stopped after a few seconds and return adapted recommendations. Users can then choose to continue incomplete simulations using the batch queuing system or go back and modify suggested options in their initial query. Detailed output provide (i) a series of low free energy structures, (ii) an online animated folding path and (iii) a programmable trajectory plot focusing on a few helices of interest to each user. The service can be accessed at

Effect of an electric field on a floating lipid bilayer: a neutron reflectivity study

We present here a neutron reflectivity study of the influence of an alternative electric field on a supported phospholipid double bilayer. We report for the first time a reproducible increase of the fluctuation amplitude leading to the complete unbinding of the floating bilayer. Results are in good agreement with a semi-quantitative interpretation in terms of negative electrostatic surface tension.Comment: 12 pages, 7 figures, 1 table accepted for publication in European Physical Journal E Replaced with with correct bibliograph

Probing complex RNA structures by mechanical force

RNA secondary structures of increasing complexity are probed combining single molecule stretching experiments and stochastic unfolding/refolding simulations. We find that force-induced unfolding pathways cannot usually be interpretated by solely invoking successive openings of native helices. Indeed, typical force-extension responses of complex RNA molecules are largely shaped by stretching-induced, long-lived intermediates including non-native helices. This is first shown for a set of generic structural motifs found in larger RNA structures, and then for Escherichia coli's 1540-base long 16S ribosomal RNA, which exhibits a surprisingly well-structured and reproducible unfolding pathway under mechanical stretching. Using out-of-equilibrium stochastic simulations, we demonstrate that these experimental results reflect the slow relaxation of RNA structural rearrangements. Hence, micromanipulations of single RNA molecules probe both their native structures and long-lived intermediates, so-called "kinetic traps", thereby capturing -at the single molecular level- the hallmark of RNA folding/unfolding dynamics.Comment: 9 pages, 9 figure

Prediction and statistics of pseudoknots in RNA structures using exactly clustered stochastic simulations

Ab initio RNA secondary structure predictions have long dismissed helices interior to loops, so-called pseudoknots, despite their structural importance. Here, we report that many pseudoknots can be predicted through long time scales RNA folding simulations, which follow the stochastic closing and opening of individual RNA helices. The numerical efficacy of these stochastic simulations relies on an O(n^2) clustering algorithm which computes time averages over a continously updated set of n reference structures. Applying this exact stochastic clustering approach, we typically obtain a 5- to 100-fold simulation speed-up for RNA sequences up to 400 bases, while the effective acceleration can be as high as 100,000-fold for short multistable molecules (<150 bases). We performed extensive folding statistics on random and natural RNA sequences, and found that pseudoknots are unevenly distributed amongst RNAstructures and account for up to 30% of base pairs in G+C rich RNA sequences (Online RNA folding kinetics server including pseudoknots : http://kinefold.u-strasbg.fr/ ).Comment: 6 pages, 5 figure

Anomalous fluctuations of active polar filaments

Using a simple model, we study the fluctuating dynamics of inextensible, semiflexible polar filaments interacting with active and directed force generating centres such as molecular motors. Taking into account the fact that the activity occurs on time-scales comparable to the filament relaxation time, we obtain some unexpected differences between both the steady-state and dynamical behaviour of active as compared to passive filaments. For the statics, the filaments have a {novel} length-scale dependent rigidity. Dynamically, we find strongly enhanced anomalous diffusion.Comment: 5 pages, 3 figure

Statistical mechanics of secondary structures formed by random RNA sequences

The formation of secondary structures by a random RNA sequence is studied as a model system for the sequence-structure problem omnipresent in biopolymers. Several toy energy models are introduced to allow detailed analytical and numerical studies. First, a two-replica calculation is performed. By mapping the two-replica problem to the denaturation of a single homogeneous RNA in 6-dimensional embedding space, we show that sequence disorder is perturbatively irrelevant, i.e., an RNA molecule with weak sequence disorder is in a molten phase where many secondary structures with comparable total energy coexist. A numerical study of various models at high temperature reproduces behaviors characteristic of the molten phase. On the other hand, a scaling argument based on the extremal statistics of rare regions can be constructed to show that the low temperature phase is unstable to sequence disorder. We performed a detailed numerical study of the low temperature phase using the droplet theory as a guide, and characterized the statistics of large-scale, low-energy excitations of the secondary structures from the ground state structure. We find the excitation energy to grow very slowly (i.e., logarithmically) with the length scale of the excitation, suggesting the existence of a marginal glass phase. The transition between the low temperature glass phase and the high temperature molten phase is also characterized numerically. It is revealed by a change in the coefficient of the logarithmic excitation energy, from being disorder dominated to entropy dominated.Comment: 24 pages, 16 figure

Self-organization of actin filament orientation in the dendritic-nucleation/array-treadmilling model

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of National Academy of Sciences of the USA for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 104 (2007): 7086-7091, doi:10.1073/pnas.0701943104.The dendritic-nucleation/array-treadmilling model provides a conceptual framework for the generation of the actin network driving motile cells. We have incorporated it into a 2-D, stochastic computer model to study lamellipodia via the self-organization of filament orientation patterns. Essential dendritic-nucleation sub-models were incorporated, including discretized actin monomer diffusion, Monte-Carlo filament kinetics, and flexible filament and plasma membrane mechanics. Model parameters were estimated from the literature and simulation, providing values for the extent of the leading edge branching/capping-protective zone (5.4 nm) and the auto-catalytic branch rate (0.43 /s). For a given set of parameters the system evolved to a steady state filament count and velocity, at which total branching and capping rates were equal only for specific orientations; net capping eliminated others. The standard parameter set evoked a sharp preference for the ±35 deg. filaments seen in lamellipodial electron micrographs, requiring ~ 12 generations of successive branching to adapt to a 15 deg. change in protrusion direction. This pattern was robust with respect to membrane surface and bending energies and to actin concentrations, but required protection from capping at the leading edge and branching angles greater than 60 deg. A +70/0/-70 deg. pattern was formed with flexible filaments ~ 100 nm or longer and with velocities less than ~ 20% of free polymerization rates

Entanglement, elasticity and viscous relaxation of actin solutions

We have investigated the viscosity and the plateau modulus of actin solutions with a magnetically driven rotating disc rheometer. For entangled solutions we observed a scaling of the plateau modulus versus concentration with a power of 7/5. The measured terminal relaxation time increases with a power 3/2 as a function of polymer length. We interpret the entanglement transition and the scaling of the plateau modulus in terms of the tube model for semiflexible polymers.Comment: 5 pages, 4 figures, published versio

A new scintillating fiber dosimeter using a single optical fiber and a CCD camera

Radiotherapy treatments become more and more accurate, using very small irradiation fields and complex dose depositions. So small dosimeters for real time and in vivo dosimetry, suitable for photons as well as for electrons beams are highly desired. In this context, a scintillating fiber dosimeter (SFD) has been developed by the Laboratoire de Physique Corpusculaire de Caen (LPC Caen), France, in collaboration with one of the French regional center for cancer treatment Centre Regional de lutte contre le cancer F. Baclesse (CRLCC F. Baclesse), Caen, France, and the ELDIM Company, Herouville, France. This plastic dosimeter is water equivalent, and it is suitable for photons as well as for electrons beams without correction. It is a real time dosimeter, with an excellent signal to noise ratio, and a spatial resolution of about a few millimeters. The aim of this study was to reduce the size of the scintillator in order to improve the spatial resolution of this dosimeter. So, a new light collection device has been developed to reduce the length of the scintillator from 1 cm to 1 mm without loss in the signal to noise ratio. The accuracy of this improved prototype has been tested by comparison with standard ionization chambers and the difference between the two devices never exceeded one percent for photon and for electron irradiation beams. A first set of commercial SFD is under completion at ELDIM and it will be soon clinically tested in several French centers for cancer treatment