137 research outputs found
Polymer compaction and bridging-induced clustering of protein-inspired patchy particles
There are many proteins or protein complexes which have multiple DNA binding
domains. This allows them to bind to multiple points on a DNA molecule (or
chromatin fibre) at the same time. There are also many proteins which have been
found to be able to compact DNA in vitro, and many others have been observed in
foci or puncta when fluorescently labelled and imaged in vivo. In this work we
study, using coarse-grained Langevin dynamics simulations, the compaction of
polymers by simple model proteins and a phenomenon known as the
"bridging-induced attraction". The latter is a mechanism observed in previous
simulations [Brackley et al., Proc. Natl. Acad. Sci. USA 110 (2013)], where
proteins modelled as spheres form clusters via their multivalent interactions
with a polymer, even in the absence of any explicit protein-protein attractive
interactions. Here we extend this concept to consider more detailed model
proteins, represented as simple "patchy particles" interacting with a
semi-flexible bead-and-spring polymer. We find that both the compacting ability
and the effect of the bridging-induced attraction depend on the valence of the
model proteins. These effects also depend on the shape of the protein, which
determines its ability to form bridges
Electrostatic inactivation of RNA viruses at air-water and liquid-liquid interfaces
Understanding the interactions between viruses and surfaces or interfaces is
important, as they provide the principles underpinning the cleaning and
disinfection of contaminated surfaces. Yet, the physics of such interactions is
currently poorly understood. For instance, there are longstanding experimental
observations suggesting that the presence of air-water interfaces can
generically inactivate and kill viruses, yet the mechanism underlying this
phenomenon remains unknown. Here we use theory and simulations to show that
electrostatics provides one such mechanism, and that this is very general.
Thus, we predict that the free energy of an RNA virus should increase by
several thousands of as the virion breaches an air-water interface. We
also show that the fate of a virus approaching a generic liquid-liquid
interface depends strongly on the detailed balance between interfacial and
electrostatic forces, which can be tuned, for instance, by choosing different
media to contact a virus-laden respiratory droplet. We propose that these
results can be used to design effective strategies for surface disinfection.
Intriguingly, tunability requires electrostatic and interfacial forces to scale
similarly with viral size, which naturally occurs when charges are arranged in
a double-shell distribution as in RNA viruses like influenza and all
coronaviruses.Comment: 10 pages, 5 figures; minor corrections to the Appendi
Chromosome compaction and chromatin stiffness enhance diffusive loop extrusion by slip-link proteins
We use Brownian dynamics simulations to study the formation of chromatin
loops through diffusive sliding of slip-link-like proteins, mimicking the
behaviour of cohesin molecules. We recently proposed that diffusive sliding is
sufficient to explain the extrusion of chromatin loops of hundreds of
kilo-base-pairs (kbp), which may then be stabilised by interactions between
cohesin and CTCF proteins. Here we show that the flexibility of the chromatin
fibre strongly affects this dynamical process, and find that diffusive loop
extrusion is more efficient on stiffer chromatin regions. We also show that the
dynamics of loop formation are faster in confined and collapsed chromatin
conformations but that this enhancement is counteracted by the increased
crowding. We provide a simple theoretical argument explaining why stiffness and
collapsed conformations favour diffusive extrusion. In light of the
heterogeneous physical and conformational properties of eukaryotic chromatin,
we suggest that our results are relevant to understand the looping and
organisation of interphase chromosomes in vivo
Non-equilibrium effects of molecular motors on polymers
We present a generic coarse-grained model to describe molecular motors acting on polymer substrates, mimicking, for example, RNA polymerase on DNA or kinesin on microtubules. The polymer is modeled as a connected chain of beads; motors are represented as freely diffusing beads which, upon encountering the substrate, bind to it through a short-ranged attractive potential. When bound, motors and polymer beads experience an equal and opposite active force, directed tangential to the polymer; this leads to motion of the motors along the polymer contour. The inclusion of explicit motors differentiates our model from other recent active polymer models. We study, by means of Langevin dynamics simulations, the effect of the motor activity on both the conformational and dynamical properties of the substrate. We find that activity leads, in addition to the expected enhancement of polymer diffusion, to an effective reduction of its persistence length. We discover that this effective "softening" is a consequence of the emergence of double-folded branches, or hairpins, and that it can be tuned by changing the number of motors or the force they generate. Finally, we investigate the effect of the motors on the probability of knot formation. Counter-intuitively our simulations reveal that, even though at equilibrium a more flexible substrate would show an increased knotting probability, motor activity leads to a marked decrease in the occurrence of knotted conformations with respect to equilibrium
Integrating transposable elements in the 3D genome
Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome
Models for twistable elastic polymers in Brownian dynamics, and their implementation for LAMMPS
An elastic rod model for semi-flexible polymers is presented. Theory for a
continuum rod is reviewed, and it is shown that a popular discretised model
used in numerical simulations gives the correct continuum limit. Correlation
functions relating to both bending and twisting of the rod are derived for both
continuous and discrete cases, and results are compared with numerical
simulations. Finally, two possible implementations of the discretised model in
the multi-purpose molecular dynamics software package LAMMPS are described.Comment: 11 pages, 4 figures; this article appeared in J. Chem. Phys. and may
be found at
http://scitation.aip.org/content/aip/journal/jcp/140/13/10.1063/1.487008
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