Discrete Breathers in a Realistic Coarse-Grained Model of Proteins

We report the results of molecular dynamics simulations of an off-lattice protein model featuring a physical force-field and amino-acid sequence. We show that localized modes of nonlinear origin (discrete breathers) emerge naturally as continuations of a subset of high-frequency normal modes residing at specific sites dictated by the native fold. In the case of the small $\beta$-barrel structure that we consider, localization occurs on the turns connecting the strands. At high energies, discrete breathers stabilize the structure by concentrating energy on few sites, while their collapse marks the onset of large-amplitude fluctuations of the protein. Furthermore, we show how breathers develop as energy-accumulating centres following perturbations even at distant locations, thus mediating efficient and irreversible energy transfers. Remarkably, due to the presence of angular potentials, the breather induces a local static distortion of the native fold. Altogether, the combination of this two nonlinear effects may provide a ready means for remotely controlling local conformational changes in proteins.Comment: Submitted to Physical Biolog

Discrete Symmetry and Stability in Hamiltonian Dynamics

In this tutorial we address the existence and stability of periodic and quasiperiodic orbits in N degree of freedom Hamiltonian systems and their connection with discrete symmetries. Of primary importance in our study are the nonlinear normal modes (NNMs), i.e periodic solutions which represent continuations of the system's linear normal modes in the nonlinear regime. We examine the existence of such solutions and discuss different methods for constructing them and studying their stability under fixed and periodic boundary conditions. In the periodic case, we employ group theoretical concepts to identify a special type of NNMs called one-dimensional "bushes". We describe how to use linear combinations such NNMs to construct s(>1)-dimensional bushes of quasiperiodic orbits, for a wide variety of Hamiltonian systems and exploit the symmetries of the linearized equations to simplify the study of their destabilization. Applying this theory to the Fermi Pasta Ulam (FPU) chain, we review a number of interesting results, which have appeared in the recent literature. We then turn to an analytical and numerical construction of quasiperiodic orbits, which does not depend on the symmetries or boundary conditions. We demonstrate that the well-known "paradox" of FPU recurrences may be explained in terms of the exponential localization of the energies Eq of NNM's excited at the low part of the frequency spectrum, i.e. q=1,2,3,.... Thus, we show that the stability of these low-dimensional manifolds called q-tori is related to the persistence or FPU recurrences at low energies. Finally, we discuss a novel approach to the stability of orbits of conservative systems, the GALIk, k=2,...,2N, by means of which one can determine accurately and efficiently the destabilization of q-tori, leading to the breakdown of recurrences and the equipartition of energy, at high values of the total energy E.Comment: 50 pages, 13 figure

Nonintegrable Schrodinger Discrete Breathers

In an extensive numerical investigation of nonintegrable translational motion of discrete breathers in nonlinear Schrodinger lattices, we have used a regularized Newton algorithm to continue these solutions from the limit of the integrable Ablowitz-Ladik lattice. These solutions are shown to be a superposition of a localized moving core and an excited extended state (background) to which the localized moving pulse is spatially asymptotic. The background is a linear combination of small amplitude nonlinear resonant plane waves and it plays an essential role in the energy balance governing the translational motion of the localized core. Perturbative collective variable theory predictions are critically analyzed in the light of the numerical results.Comment: 42 pages, 28 figures. to be published in CHAOS (December 2004

Breather lattice and its stabilization for the modified Korteweg-de Vries equation

We obtain an exact solution for the breather lattice solution of the modified Korteweg-de Vries (MKdV) equation. Numerical simulation of the breather lattice demonstrates its instability due to the breather-breather interaction. However, such multi-breather structures can be stabilized through the concurrent application of ac driving and viscous damping terms.Comment: 6 pages, 3 figures, Phys. Rev. E (in press

Malocclusion and rhinitis in children: an easy-going relationship or a yet to be resolved paradox? A systematic literature revision

Objective: The relation between nasal flow and malocclusion represents a practical concern to pediatricians, otorhinolaryngologists, orthodontists, allergists and speech therapists. If naso-respiratory function may influence craniofacial growth is still debated. Chronic mouth-breathing is reported to be associated also with a characteristic pattern of dental occlusion. On the other hand, also malocclusion may reduce nasal air flows promoting nasal obstruction. Hereby, the aim of this review was to describe the relationship between rhinitis and malocclusion in children. Methods: An electronic search was conducted using online database including Pubmed, Web of Science, Google Scholar and Embase. All studies published through to January 30, 2017 investigating the prevalence of malocclusion in children and adolescents (aged 0-20 years) affected by rhinitis and the prevalence of rhinitis in children with malocclusion were included. The protocol was registered at PROSPERO - International prospective register of systematic reviews under CRD42016053619. Results: Ten studies with 2733 patients were included in the analysis. The prevalence of malocclusion in children with rhinitis was specified in four of the studies ranging from as high as 78.2% to as low as 3%. Two out of the studies reported the prevalence of rhinitis in children with malocclusion with a rate ranging from 59.2 to 76.4%. Conclusion: The results of this review underline the importance of the diagnosis and treatment of the nasal obstruction at an early age to prevent an altered facial growth, but the data currently available on this topic do not allow to establish a possible causal relationship between rhinitis and malocclusion

Nonlinear waves in Newton's cradle and the discrete p-Schroedinger equation

We study nonlinear waves in Newton's cradle, a classical mechanical system consisting of a chain of beads attached to linear pendula and interacting nonlinearly via Hertz's contact forces. We formally derive a spatially discrete modulation equation, for small amplitude nonlinear waves consisting of slow modulations of time-periodic linear oscillations. The fully-nonlinear and unilateral interactions between beads yield a nonstandard modulation equation that we call the discrete p-Schroedinger (DpS) equation. It consists of a spatial discretization of a generalized Schroedinger equation with p-Laplacian, with fractional p>2 depending on the exponent of Hertz's contact force. We show that the DpS equation admits explicit periodic travelling wave solutions, and numerically find a plethora of standing wave solutions given by the orbits of a discrete map, in particular spatially localized breather solutions. Using a modified Lyapunov-Schmidt technique, we prove the existence of exact periodic travelling waves in the chain of beads, close to the small amplitude modulated waves given by the DpS equation. Using numerical simulations, we show that the DpS equation captures several other important features of the dynamics in the weakly nonlinear regime, namely modulational instabilities, the existence of static and travelling breathers, and repulsive or attractive interactions of these localized structures

Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function. Hypotheses and a comprehensive review

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into ‘cumulus-type’, i.e., those similar to puffy (white) clouds, and ‘stratus-type’, i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an ‘energy transfer’ mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by ‘multi-trajectories’; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach ‘rarely visited’ but functionally-related states. We also show the role of disorder in ‘spatial games’ of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks

Energy transfer in nonlinear network models of proteins

We investigate how nonlinearity and topological disorder affect the energy relaxation of local kicks in coarse-grained network models of proteins. We find that nonlinearity promotes long-range, coherent transfer of substantial energy to specific, functional sites, while depressing transfer to generic locations. Remarkably, transfer can be mediated by the self-localization of discrete breathers at distant locations from the kick, acting as efficient energy-accumulating centers.Comment: 4 pages, 3 figure

Cooperative surmounting of bottlenecks

The physics of activated escape of objects out of a metastable state plays a key role in diverse scientific areas involving chemical kinetics, diffusion and dislocation motion in solids, nucleation, electrical transport, motion of flux lines superconductors, charge density waves, and transport processes of macromolecules, to name but a few. The underlying activated processes present the multidimensional extension of the Kramers problem of a single Brownian particle. In comparison to the latter case, however, the dynamics ensuing from the interactions of many coupled units can lead to intriguing novel phenomena that are not present when only a single degree of freedom is involved. In this review we report on a variety of such phenomena that are exhibited by systems consisting of chains of interacting units in the presence of potential barriers. In the first part we consider recent developments in the case of a deterministic dynamics driving cooperative escape processes of coupled nonlinear units out of metastable states. The ability of chains of coupled units to undergo spontaneous conformational transitions can lead to a self-organised escape. The mechanism at work is that the energies of the units become re-arranged, while keeping the total energy conserved, in forming localised energy modes that in turn trigger the cooperative escape. We present scenarios of significantly enhanced noise-free escape rates if compared to the noise-assisted case. The second part deals with the collective directed transport of systems of interacting particles overcoming energetic barriers in periodic potential landscapes. Escape processes in both time-homogeneous and time-dependent driven systems are considered for the emergence of directed motion. It is shown that ballistic channels immersed in the associated high-dimensional phase space are the source for the directed long-range transport