Antonio Suma

How to fold intricately: using theory and experiments to unravel the properties of knotted proteins.

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native state. Here, we review such developments by paying particular attention to the complementarity of experimental and computational studies. Key open issues that could be tackled with either or both approaches are finally pointed out.

Dynamics of a homogeneous active dumbbell system

We analyze the dynamics of a two-dimensional system of interacting active dumbbells. We characterize the mean-square displacement, linear response function, and deviation from the equilibrium fluctuation-dissipation theorem as a function of activity strength, packing fraction, and temperature for parameters such that the system is in its homogeneous phase. While the diffusion constant in the last diffusive regime naturally increases with activity and decreases with packing fraction, we exhibit an intriguing nonmonotonic dependence on the activity of the ratio between the finite-density and the single-particle diffusion constants. At fixed packing fraction, the time-integrated linear response function depends nonmonotonically on activity strength. The effective temperature extracted from the ratio between the integrated linear response and the mean-square displacement in the last diffusive regime is always higher than the ambient temperature, increases with increasing activity, and, for small active force, monotonically increases with density while for sufficiently high activity it first increases and next decreases with the packing fraction. We ascribe this peculiar effect to the existence of finite-size clusters for sufficiently high activity and density at the fixed (low) temperatures at which we worked. The crossover occurs at lower activity or density the lower the external temperature. The finite-density effective temperature is higher (lower) than the single dumbbell one below (above) a crossover value of the Péclet number.

Pore translocation of knotted DNA rings

Significance Pore translocation, the driven passage of molecules through narrow channels, has become an important tool for probing DNA properties. In a recent breakthrough experiment, this technique was used to detect knots that form spontaneously in DNA filaments and can hence impact their in vivo functionality. Here, by using an accurate model, we simulate the translocation of knotted DNA, expose its unexpectedly rich phenomenology, and clarify the implications for experiments. We show that knot translocation occurs in two possible modes, depending on the knot initial position and size. These properties also account for the typically late occurrence of the knot passage event. Finally, the passage duration is found to depend more on the translocation velocity of the knot than its size. We use an accurate coarse-grained model for DNA and stochastic molecular dynamics simulations to study the pore translocation of 10-kbp–long DNA rings that are knotted. By monitoring various topological and physical observables we find that there is not one, as previously assumed, but rather two qualitatively different modes of knot translocation. For both modes the pore obstruction caused by knot passage has a brief duration and typically occurs at a late translocation stage. Both effects are well in agreement with experiments and can be rationalized with a transparent model based on the concurrent tensioning and sliding of the translocating knotted chains. We also observed that the duration of the pore obstruction event is more controlled by the knot translocation velocity than the knot size. These features should advance the interpretation and design of future experiments aimed at probing the spontaneous knotting of biopolymers.

Phase segregation in a system of active dumbbells

A systems of self-propelled dumbbells interacting by a Weeks–Chandler–Anderson potential is considered. At sufficiently low temperatures the system phase separates into a dense phase and a gas-like phase. The kinetics of the cluster formation and the growth law for the average cluster size are analyzed.

Motility-induced phase separation and coarsening in active matter

Abstract Active systems, or active matter, are self-driven systems that live, or function, far from equilibrium – a paradigmatic example that we focus on here is provided by a suspension of self-motile particles. Active systems are far from equilibrium because their microscopic constituents constantly consume energy from the environment in order to do work, for instance to propel themselves. The non-equilibrium nature of active matter leads to a variety of non-trivial intriguing phenomena. An important one, which has recently been the subject of intense interest among biological and soft matter physicists, is that of the so-called “motility-induced phase separation”, whereby self-propelled particles accumulate into clusters in the absence of any explicit attractive interactions between them. Here we review the physics of motility-induced phase separation, and discuss this phenomenon within the framework of the classic physics of phase separation and coarsening. We also discuss theories for bacterial colonies where coarsening may be arrested. Most of this work will focus on the case of run-and-tumble and active Brownian particles in the absence of solvent-mediated hydrodynamic interactions – we will briefly discuss at the end their role, which is not currently fully understood in this context.

Fluctuations of rotational and translational degrees of freedom in an interacting active dumbbell system

Abstract We study the dynamical properties of a two-dimensional ensemble of self-propelled dumbbells with only repulsive interactions. After summarizing the behavior of the translational and rotational mean-square displacements in the homogeneous phase that we established in a previous study, we analyze their fluctuations. We study the dependence of the probability distribution functions in terms of the Peclet number, describing the relative role of active forces and thermal fluctuations, and of particle density.

Large Fluctuations and Dynamic Phase Transition in a System of Self-Propelled Particles

We study the statistics, in stationary conditions, of the work W_{τ} done by the active force in different systems of self-propelled particles in a time τ. We show the existence of a critical value W_{τ}^{†} such that fluctuations with W_{τ}>W_{τ}^{†} correspond to configurations where interaction between particles plays a minor role whereas those with W_{τ}<W_{τ}^{†} represent states with single particles dragged by clusters. This twofold behavior is fully mirrored by the probability distribution P(W_{τ}) of the work, which does not obey the large-deviation principle for W_{τ}<W_{τ}^{†}. This pattern of behavior can be interpreted as due to a phase transition occurring at the level of fluctuating quantities and an order parameter is correspondingly identified.

Phase Coexistence in Two-Dimensional Passive and Active Dumbbell Systems

We demonstrate that there is a macroscopic coexistence between regions with hexatic order and regions in the liquid or gas phase over a finite interval of packing fractions in active dumbbell systems with repulsive power-law interactions in two dimensions. In the passive limit, this interval remains finite, similar to what has been found in two-dimensional systems of hard and soft disks. We did not find discontinuous behavior upon increasing activity from the passive limit.

Dynamics of supercoiled DNA with complex knots: large-scale rearrangements and persistent multi-strand interlocking

Abstract Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. While the effects on plasmid organization has been extensively studied for knotting and supercoiling taken separately, much less is known about their concurrent action. Here, we use molecular dynamics simulations and oxDNA, an accurate mesoscopic DNA model, to study the kinetic and metric changes introduced by complex (five-crossing) knots and supercoiling in 2 kbp-long DNA rings. We find several unexpected results. First, the conformational ensemble is dominated by two distinct states, differing in branchedness and knot size. Secondly, fluctuations between these states are as fast as the metric relaxation of unknotted rings. In spite of this, certain boundaries of knotted and plectonemically-wound regions can persist over much longer timescales. These pinned regions involve multiple strands that are interlocked by the cooperative action of topological and supercoiling constraints. Their long-lived character may be relevant for the simplifying action of topoisomerases.

Active dumbbells: Dynamics and morphology in the coexisting region

Abstract.With the help of molecular dynamics simulations we study an ensemble of active dumbbells in purely repulsive interaction. We derive the phase diagram in the density-activity plane and we characterise the various phases with liquid, hexatic and solid character. The analysis of the structural and dynamical properties, such as enstrophy, mean-square displacement, polarisation, and correlation functions, shows the continuous character of liquid and hexatic phases in the coexisting region when the activity is increased starting from the passive limit.Graphical abstract