Directional translocation resistance of Zika xrRNA

xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, 5 \u2032 and 3 \u2032, are driven through a pore. Pulling the 3 \u2032 end, as done by replicases, elicits a progressive unfolding; pulling the 5 \u2032 end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the 5 \u2032 end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials

Accurate sampling using Langevin dynamics

We show how to derive a simple integrator for the Langevin equation and illustrate how it is possible to check the accuracy of the obtained distribution on the fly, using the concept of effective energy introduced in a recent paper [J. Chem. Phys. 126, 014101 (2007)]. Our integrator leads to correct sampling also in the difficult high-friction limit. We also show how these ideas can be applied in practical simulations, using a Lennard-Jones crystal as a paradigmatic case

Does Ménière's Disease in the Elderly Present Some Peculiar Features?

Object. Aim of our study was to establish some peculiar features of Ménière's Disease (MD) in a group of elderly MD patients, in which the first vertigo spell happened when over 65 years old. Material and Methods. We analyzed a group of 73 younger than 65-years-old and a group of 30 elderly MD patients. All patients underwent a neurotological evaluation, an anamnestic evaluation including a lifetime history of migraine, and blood withdrawal for autoantibody screening. Results. Some differences were found between elderly and younger MD patients. Elderly MD patients presented a higher prevalence of Tumarkin attacks and a lower prevalence of lifetime history of migraine; moreover, they presented a faster develop of hearing loss and vertigo spells than a subgroup of 32 younger patients matched for the duration of illness. Conclusions. Some clinical features of MD in elderly have been pointed out. Particularly, the lower rate of migrainous history and positivity for autoantibodies often associated with MD, in our opinion, support the hypothesis of a vascular disorder acting as a predisposing factor for MD in elderly

Colored-noise thermostats \`a la carte

Recently, we have shown how a colored-noise Langevin equation can be used in the context of molecular dynamics as a tool to obtain dynamical trajectories whose properties are tailored to display desired sampling features. In the present paper, after having reviewed some analytical results for the stochastic differential equations forming the basis of our approach, we describe in detail the implementation of the generalized Langevin equation thermostat and the fitting procedure used to obtain optimal parameters. We discuss in detail the simulation of nuclear quantum effects, and demonstrate that, by carefully choosing parameters, one can successfully model strongly anharmonic solids such as neon. For the reader's convenience, a library of thermostat parameters and some demonstrative code can be downloaded from an on-line repository

Fitting Corrections to an RNA Force Field Using Experimental Data

Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude

Interchain interaction and Davydov splitting in polythiophene crystals: An ab initio approach

The crystal-induced energy splitting of the lowest excitonic state in polymer crystals, the so-called Davydov splitting Δ, is calculated with a first-principles density-matrix scheme. We show that different crystalline arrangements lead to significant variations in Δ, from below to above the thermal energy kBT at room temperature, with relevant implications on the luminescence efficiency. This is one more piece of evidence supporting the fact that control of interchain interactions and solid-state packing is essential for the design of efficient optical devices

Conjugate gradient heatbath for ill-conditioned actions

We present a method for performing sampling from a Boltzmann distribution of an ill-conditioned quadratic action. This method is based on heatbath thermalization along a set of conjugate directions, generated via a conjugate-gradient procedure. The resulting scheme outperforms local updates for matrices with very high condition number, since it avoids the slowing down of modes with lower eigenvalue, and has some advantages over the global heatbath approach, compared to which it is more stable and allows for more freedom in devising case-specific optimizations