Properties of low-dimensional collective variables in the molecular dynamics of biopolymers

The description of the dynamics of a complex, high-dimensional system in terms of a low-dimensional set of collective variables Y can be fruitful if the low dimensional representation satisfies a Langevin equation with drift and diffusion coefficients which depend only on Y. We present a computational scheme to evaluate whether a given collective variable provides a faithful low-dimensional representation of the dynamics of a high-dimensional system. The scheme is based on the framework of finite-difference Langevin-equation, similar to that used for molecular-dynamics simulations. This allows one to calculate the drift and diffusion coefficients in any point of the full-dimensional system. The width of the distribution of drift and diffusion coefficients in an ensemble of microscopic points at the same value of Y indicates to which extent the dynamics of Y is described by a simple Langevin equation. Using a simple protein model we show that collective variables often used to describe biopolymers display a non-negligible width both in the drift and in the diffusion coefficients. We also show that the associated effective force is compatible with the equilibrium free--energy calculated from a microscopic sampling, but results in markedly different dynamical properties

Metadynamic sampling of the free energy landscapes of proteins coupled with a Monte Carlo algorithm

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus to gain an ever-increasing understanding on the general principles underlying the mechanism of protein folding. We show that it is possible to couple metadynamics and Monte Carlo algorithms to obtain the free energy of model proteins in a way which is computationally very economical.Comment: Submitted to Gen

Why should DNA topoisomerase i have a scaffold activity?

Since the early 1990s, in vitro studies have demonstrated that DNA topoisomerase I pro-motes RNA polymerase II transcription, acting as a cofactor, regardless of its catalytic activity. Recent studies, carried in vivo, using yeast as a model system, also demonstrate that DNA topoisomerase I is able to recruit, without the involvement of its catalytic activity, the Sir2p deacetylase on ribosomal genes thus contributes to achieve their silencing. In this review, the DNA topoisomerase I capability, acting as a scaffold protein, as well as its involvement and role in several macromolecular complexes, will be discussed, in light of several observations reported in the literature, pointing out how its role goes far beyond its well-known ability to relax DNA

What is a Gene? A Two Sided View

The need to account for all currently available experimental observations concerning the gene nature, has reshaped the concept of gene turning it from the essentially mechanistic unit, predominant during the '70s, into a quite abstract open and generalized entity, whose contour appears less defined as compared to the past. Here we propose the essence of the gene to be considered double faced. In this respect genotypic and phenotypic entities of a gene would coexist and mix reciprocally. This harmonizes present knowledge with current definitions and predisposes for remodelling of our thinking as a consequence of future discoveries. A two sided view of the gene also allows to combine the genetic and epigenetic aspects in a unique solution, being structural and functional at the same time and simultaneously able to include the different levels in an overlapping unicum

Force-free magnetosphere attractors for near-horizon extreme and near-extreme limits of Kerr black hole

We propose a new approach to find magnetically-dominated force-free magnetospheres around highly spinning black holes, relevant for models of astrophysical jets. Employing the near-horizon extreme Kerr (NHEK) limit of the Kerr black hole, any stationary, axisymmetric and regular force-free magnetosphere reduces to the same attractor solution in the NHEK limit with null electromagnetic field strength. We use this attractor solution as the universal starting point for perturbing away from the NHEK region in the extreme Kerr spacetime. We demonstrate that by going to second order in perturbation theory, it is possible to find magnetically dominated magnetospheres around the extreme Kerr black hole. Furthermore, we consider the near-horizon near-extreme Kerr (near-NHEK) limit that provides access to a different regime of highly spinning black holes. Also in this case we find a novel force-free attractor, which can be used as the universal starting point for a perturbative construction of force-free magnetospheres. Finally, we discuss the relation between the NHEK and near-NHEK attractors.Comment: 5 pages, 1 figur

Moving away from the Near-Horizon Attractor of the Extreme Kerr Force-Free Magnetosphere

We consider force-free magnetospheres around the extreme Kerr black hole. In this case there is no known exact analytic solution to force free electrodynamics which is stationary, axisymmetric and magnetically-dominated. However, any stationary, axisymmetric and regular force-free magnetosphere in extreme Kerr black hole approaches the same attractor solution in the near-horizon extreme Kerr (NHEK) limit with null electromagnetic field. We show that by moving away from the attractor solution in the NHEK region, one finds magnetically-dominated solutions in the extreme Kerr black hole with finite angular momentum outflow. This result is achieved using a perturbative analysis up to the second order.Comment: 33 pages, 2 figures; v2: matches published version in JCA

Hierarchy of folding and unfolding events of protein G, CI2, and ACBP from explicit-solvent simulations

The study of the mechanism which is at the basis of the phenomenon of protein folding requires the knowledge of multiple folding trajectories under biological conditions. Using a biasing molecular-dynamics algorithm based on the physics of the ratchet-and-pawl system, we carry out all-atom, explicit solvent simulations of the sequence of folding events which proteins G, CI2, and ACBP undergo in evolving from the denatured to the folded state. Starting from highly disordered conformations, the algorithm allows the proteins to reach, at the price of a modest computational effort, nativelike conformations, within a root mean square deviation (RMSD) of approximately 1 . A scheme is developed to extract, from the myriad of events, information concerning the sequence of native contact formation and of their eventual correlation. Such an analysis indicates that all the studied proteins fold hierarchically, through pathways which, although not deterministic, are well-defined with respect to the order of contact formation. The algorithm also allows one to study unfolding, a process which looks, to a large extent, like the reverse of the major folding pathway. This is also true in situations in which many pathways contribute to the folding process, like in the case of protein G

SRG/eROSITA and XMM-Newton observations of Vela Jr

The Vela supernova remnant complex is a region containing at least three supernova remnants: Vela, Puppis A, and Vela Jr. With the launch of the spectro-imaging X-ray telescope eROSITA on board the Spectrum Roentgen Gamma (SRG) mission, it became possible to observe the one degree wide Vela Jr in its entirety. Although several previous pointed Chandra and XMM-Newton observations are available, it is only the second time after the ROSAT all-sky survey that the whole remnant was observed in X-rays with homogeneous sensitivity. Vela Jr is one of the few remnants emitting in the TeV band, making it an important object in shock acceleration studies. However, the age and distance determination using X-ray emission is largely hampered by the presence of the Vela SNR along the same line. With the eROSITA data set our aim is to characterize the emission of Vela Jr and distinguish it from Vela emission, and also to characterize the spectral emission of the inner remnant. We processed the eROSITA data dividing the whole remnant into seven different regions. In addition, images of the whole remnant were employed to pinpoint the position of the geometric center and constrain the proper motion of the CCO. We also employed archival XMM-Newton pointed observations of the NW rim to determine the cutoff energy of the electrons and the expansion velocity. We find the magnetic field can vary between 2 $\mu$G and 16 $\mu$G in the NW rim. We also find that the remnant spectrum is uniformly featureless in most regions, except for two inner regions where an extra thermal model component improves the fit. We obtain new coordinates for the geometric remnant center, resulting in a separation of only 35.2 $\pm$ 15.8" from the position of the CCO. As a result, we reinforce the association between the CCO and a proposed faint optical/IR counterpart.Comment: Accepted for publication in A&