Folding kinetics of an entangled protein.

The possibility of the protein backbone adopting lasso-like entangled motifs has attracted increasing attention. After discovering the surprising abundance of natively entangled protein domain structures, it was shown that misfolded entangled subpopulations might become thermosensitive or escape the homeostasis network just after translation. To investigate the role of entanglement in shaping folding kinetics, we introduce a novel indicator and analyze simulations of a coarse-grained, structure-based model for two small single-domain proteins.

Interpretable Machine Learning of Amino Acid Patterns in Proteins: A Statistical Ensemble Approach.

Explainable and interpretable unsupervised machine learning helps one to understand the underlying structure of data. We introduce an ensemble analysis of machine learning models to consolidate their interpretation. Its application shows that restricted Boltzmann machines compress consistently into a few bits the information stored in a sequence of five amino acids at the start or end of α-helices or β-sheets.

Radiomics and deep learning methods for the prediction of 2-year overall survival in LUNG1 dataset.

In this study, we tested and compared radiomics and deep learning-based approaches on the public LUNG1 dataset, for the prediction of 2-year overall survival (OS) in non-small cell lung cancer patients. Radiomic features were extracted from the gross tumor volume using Pyradiomics, while deep features were extracted from bi-dimensional tumor slices by convolutional autoencoder. Both radiomic and deep features were fed to 24 different pipelines formed by the combination of four feature selection/reduction methods and six classifiers.

Dynamic and facilitated binding of topoisomerase accelerates topological relaxation.

How type 2 Topoisomerase (TopoII) proteins relax and simplify the topology of DNA molecules is one of the most intriguing open questions in genome and DNA biophysics. Most of the existing models neglect the dynamics of TopoII which is expected of proteins searching their targets via facilitated diffusion. Here, we show that dynamic binding of TopoII speeds up the topological relaxation of knotted substrates by enhancing the search of the knotted arc.

Generalized virial equation for nonlinear multiplicative Langevin dynamics: Application to laser-cooled atoms.

The virial theorem, and the equipartition theorem in the case of quadratic degrees of freedom, are handy constraints on the statistics of equilibrium systems. Their violation is instrumental in determining how far from equilibrium a driven system might be. We extend the virial theorem to nonequilibrium conditions for Langevin dynamics with nonlinear friction and multiplicative noise.

The rise and fall of branching: A slowing down mechanism in relaxing wormlike micellar networks.

A mean-field kinetic model suggests that the relaxation dynamics of wormlike micellar networks is a long and complex process due to the problem of reducing the number of free end-caps (or dangling ends) while also reaching an equilibrium level of branching after an earlier overgrowth. The model is validated against mesoscopic molecular dynamics simulations and is based on kinetic equations accounting for scission and synthesis processes of blobs of surfactants. A long relaxation time scale is reached with both thermal quenches and small perturbations of the system.

Aging of living polymer networks: a model with patchy particles.

Microrheology experiments show that viscoelastic media composed by wormlike micellar networks display complex relaxations lasting seconds even at the scale of micrometers. By mapping a model of patchy colloids with suitable mesoscopic elementary motifs to a system of worm-like micelles, we are able to simulate its relaxation dynamics, upon a thermal quench, spanning many decades, from microseconds up to tens of seconds. After mapping the model to real units and to experimental scission energies, we show that the relaxation process develops through a sequence of non-local and energetically challenging arrangements.

Folding Rate Optimization Promotes Frustrated Interactions in Entangled Protein Structures.

Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in structural biology. Recently, the hypothesis that energetic frustration might be a mechanism to avoid topological frustration has been put forward based on the empirical observation that loops involved in entanglements are stabilized by weak interactions between amino-acids at their extrema.

Sequence and structural patterns detected in entangled proteins reveal the importance of co-translational folding.

Proteins must fold quickly to acquire their biologically functional three-dimensional native structures. Hence, these are mainly stabilized by local contacts, while intricate topologies such as knots are rare. Here, we reveal the existence of specific patterns adopted by protein sequences and structures to deal with backbone self-entanglement.

Topological Sieving of Rings According to Their Rigidity.

We present a novel mechanism for resolving the mechanical rigidity of nanoscopic circular polymers that flow in a complex environment. The emergence of a regime of negative differential mobility induced by topological interactions between the rings and the substrate is the key mechanism for selective sieving of circular polymers with distinct flexibilities. A simple model accurately describes the sieving process observed in molecular dynamics simulations and yields experimentally verifiable analytical predictions, which can be used as a reference guide for improving filtration procedures of circular filaments.

Linking in domain-swapped protein dimers.

The presence of knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The exchanging of identical structural elements, typical of domain-swapped proteins, makes such dimers suitable candidates to validate the possibility that mutual entanglement between chains may play a similar role for protein complexes. We suggest that such entanglement is captured by the linking number.

Self-similar aftershock rates.

In many important systems exhibiting crackling noise-an intermittent avalanchelike relaxation response with power-law and, thus, self-similar distributed event sizes-the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is particularly true for the case of seismicity, and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features.

Thermal response of nonequilibrium RC circuits.

We analyze experimental data obtained from an electrical circuit having components at different temperatures, showing how to predict its response to temperature variations. This illustrates in detail how to utilize a recent linear response theory for nonequilibrium overdamped stochastic systems. To validate these results, we introduce a reweighting procedure that mimics the actual realization of the perturbation and allows extracting the susceptibility of the system from steady-state data.

Inflow rate, a time-symmetric observable obeying fluctuation relations.

While entropy changes are the usual subject of fluctuation theorems, we seek fluctuation relations involving time-symmetric quantities, namely observables that do not change sign if the trajectories are observed backward in time. We find detailed and integral fluctuation relations for the (time-integrated) difference between entrance rate and escape rate in mesoscopic jump systems. Such inflow rate, which is even under time reversal, represents the discrete-state equivalent of the phase-space contraction rate.

Role of trapping and crowding as sources of negative differential mobility.

Increasing the crowding in an environment does not necessarily trigger negative differential mobility of strongly pushed particles. Moreover, the choice of the model, in particular the kind of microscopic jump rates, may be very relevant in determining the mobility. We support these points via simple examples and we therefore address recent claims saying that crowding in an environment is likely to promote negative differential mobility.

Energy repartition for a harmonic chain with local reservoirs.

We exactly analyze the vibrational properties of a chain of harmonic oscillators in contact with local Langevin heat baths. Nonequilibrium steady-state fluctuations are found to be described by a set of mode temperatures, independent of the strengths of both the harmonic interaction and the viscous damping. Energy is equally distributed between the conjugate variables of a given mode but differently among different modes, in a manner which depends exclusively on the bath temperatures and on the boundary conditions.

Rings in random environments: sensing disorder through topology.

In this paper we study the role of topology in DNA gel electrophoresis experiments via molecular dynamics simulations. The gel is modelled as a 3D array of obstacles from which half edges are removed at random with probability p, thereby generating a disordered environment. Changes in the microscopic structure of the gel are captured by measuring the electrophoretic mobility of ring polymers moving through the medium, while their linear counterparts provide a control system as we show they are insensitive to these changes.

First-order coil-globule transition driven by vibrational entropy.

By shifting the balance between conformational entropy and internal energy, polymers modify their shape under external stimuli, such as changes in temperature. Prominent among such transformations is the coil-globule transition, whereby a polymer can switch from an entropy-dominated coil conformation to a globular one, governed by energy. The nature of the coil-globule transition has remained elusive, with evidence for both continuous and discontinuous transitions, with the two-state behaviour of proteins as an instance of the latter.

Fibril elongation mechanisms of HET-s prion-forming domain: topological evidence for growth polarity.

The prion-forming C-terminal domain of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. The conformational switch from the nonprion soluble form to the prion fibrillar form is believed to have a functional role, as HET-s in its prion form participates in a recognition process of different fungal strains. On the basis of the knowledge of the high-resolution structure of the prion forming domain HET-s(218-289) in its fibrillar form, we here present a numerical simulation of the fibril growth process, which emphasizes the role of the topological properties of the fibrillar structure.

Interplay between writhe and knotting for swollen and compact polymers.

The role of the topology and its relation with the geometry of biopolymers under different physical conditions is a nontrivial and interesting problem. Aiming at understanding this issue for a related simpler system, we use Monte Carlo methods to investigate the interplay between writhe and knotting of ring polymers in good and poor solvents. The model that we consider is interacting self-avoiding polygons on the simple cubic lattice.

Fluctuations and response of nonequilibrium states.

A generalized fluctuation-response relation is found for thermal systems driven out of equilibrium. Its derivation is independent of many details of the dynamics, which is only required to be first order. The result gives a correction to the equilibrium fluctuation-dissipation theorem, in terms of the correlation between observable and excess in dynamical activity caused by the perturbation.

Graph theoretical analysis of the energy landscape of model polymers.

In systems characterized by a rough potential-energy landscape, local energetic minima and saddles define a network of metastable states whose topology strongly influences the dynamics. Changes in temperature, causing the merging and splitting of metastable states, have nontrivial effects on such networks and must be taken into account. We do this by means of a recently proposed renormalization procedure.

Fluctuation symmetries for work and heat.

We consider a particle dragged through a medium at constant temperature as described by a Langevin equation with a time-dependent potential. The time dependence is specified by an external protocol. We give conditions on potential and protocol under which the fluctuations of the dissipative work satisfy an exact symmetry for all times.

Self-organized-criticality model consistent with statistical properties of edge turbulence in a fusion plasma.

The statistical properties of the intermittent signal generated by a recent model for self-organized criticality are examined. A successful comparison is made with previously published results of the equivalent quantities measured in the electrostatic turbulence at the edge of a fusion plasma. This result reestablishes self-organized criticality as a potential paradigm for transport in magnetic fusion devices, overriding shortcomings pointed out in earlier works [E.