arXiv subjects

Jaeoh Shin

Publications and source records attributed to Jaeoh Shin.

14 recordsLinked to original sources

arXiv2021

Crowding breaks the forward/backward symmetry of transition times in biased random walks

Microscopic mechanisms of natural processes are frequently understood in terms of random walk models by analyzing local particle transitions. This is because these models properly account for dynamic processes at the molecular level and provide a clear physical picture. Recent theoretical studies made a surprising discovery that in complex systems the symmetry of molecular forward/backward transition times with respect to local bias in the dynamics may be broken and it may take longer to go downhill than uphill. The physical origins of these phenomena remain not fully understood. Here we explore in more detail the microscopic features of the symmetry breaking in the forward/backward transition times by analyzing exactly solvable discrete-state stochastic models. In particular, we consider a specific case of two random walkers on four-sites periodic lattice as the way to represent the general systems with multiple pathways. It is found that the asymmetry in transition times depends on several factors that include the degree of deviation from equilibrium, the particle crowding and methods of measurements of dynamic properties. Our theoretical analysis suggests that the asymmetry in transition times can be explored experimentally for determining the important microscopic features of natural processes by quantitative measuring the local deviations from equilibrium and the degrees of crowding.

cond-mat.stat-mech↗

arXiv2020

Asymmetry of forward/backward transition times as a non-equilibrium measure of complexity of microscopic mechanisms

In one-dimensional random walks, the waiting time for each direction transitions is the same, even in the presence of bias, as a consequence of the microscopic-reversibility. We study the symmetry breaking of forward/ backward transition times in a random walk on a lattice of two lanes. We find that either transition times can be faster depending on the lattice's net current, and the symmetry is recovered only at equilibrium. Our analysis suggests that the forward/ backward transition times' asymmetry can be used as a measure of deviation from the equilibrium of the system.

cond-mat.stat-mech↗

arXiv2019

The Effect of Obstacles in Multi-Site Protein Target Search with DNA Looping

Many fundamental biological processes are regulated by protein-DNA complexes called {\it synaptosomes}, which possess multiple interaction sites. Despite the critical importance of synaptosomes, the mechanisms of their formation remain not well understood. Because of the multi-site nature of participating proteins, it is widely believed that their search for specific sites on DNA involves the formation and breaking of DNA loops and sliding in the looped configurations. In reality, DNA in live cells is densely covered by other biological molecules that might interfere with the formation of synaptosomes. In this work, we developed a theoretical approach to evaluate the role of obstacles in the target search of multi-site proteins when the formation of DNA loops and the sliding in looped configurations are possible. Our theoretical method is based on analysis of a discrete-state stochastic model that uses a master equations approach and extensive computer simulations. It is found that the obstacle slows down the search dynamics in the system when DNA loops are long-lived, but the effect is minimal for short-lived DNA loops. In addition, the relative positions of the target and the obstacle strongly influence the target search kinetics. Furthermore, the presence of the obstacle might increase the noise in the system. These observations are discussed using physical-chemical arguments. Our theoretical approach clarifies the molecular mechanisms of formation of protein-DNA complexes with multiple interactions sites.

cond-mat.soft↗

arXiv2019

Target search on DNA by interacting molecules: First-passage approach

Gene regulation is one of the most important fundamental biological processes in living cells. It involves multiple protein molecules that locate specific sites on DNA and assemble gene initiation or gene repression multi-molecular complexes. While the protein search dynamics for DNA targets has been intensively investigated, the role of inter-molecular interactions during the genetic activation or repression remains not well quantified. Here we present a simple one-dimensional model of target search for two interacting molecules that can reversibly form a dimer molecular complex, which also participates in the search process. In addition, the proteins have finite residence times on specific target sites, and the gene is activated or repressed when both proteins are simultaneously present at the target. The model is analyzed using first-passage analytical calculations and Monte Carlo computer simulations. It is shown that the search dynamics exhibits a complex behavior depending on the strength of inter-molecular interactions and on the target residence times. We also found that the search time shows a non-monotonic behavior as a function of the dissociation rate for the molecular complex. Physical-chemical arguments to explain these observations are presented. Our theoretical approach highlights the importance of molecular interactions in the complex process of gene activation/repression by multiple transcription factor proteins.

physics.bio-ph↗

arXiv2019

Facilitation of DNA loop formation by protein-DNA non-specific interactions

Complex DNA topological structures, including polymer loops, are frequently observed in biological processes when protein molecules simultaneously bind to several distant sites on DNA. However, the molecular mechanisms of formation of these systems remain not well understood. Existing theoretical studies focus only on specific interactions between protein and DNA molecules at target sequences. However, the electrostatic origin of primary protein-DNA interactions suggests that interactions of proteins with all DNA segments should be considered. Here we theoretically investigate the role of non-specific interactions between protein and DNA molecules on the dynamics of loop formation. Our approach is based on analyzing a discrete-state stochastic model via a method of first-passage probabilities supplemented by Monte Carlo computer simulations. It is found that depending on a protein sliding length during the non-specific binding event three different dynamic regimes of the DNA loop formation might be observed. In addition, the loop formation time might be optimized by varying the protein sliding length, the size of the DNA molecule, and the position of the specific target sequences on DNA. Our results demonstrate the importance of non-specific protein-DNA interactions in the dynamics of DNA loop formations. Several quantitative predictions that can be experimentally tested are also presented.

cond-mat.soft↗

arXiv2018

Molecular search with conformational change: One-dimensional discrete-state stochastic model

Molecular search phenomena are observed in a variety of chemical and biological systems. During the search the participating particles frequently move in complex inhomogeneous environments with random transitions between different dynamic modes. To understand the mechanisms of molecular search with alternating dynamics, we investigate the search dynamics with stochastic transitions between two conformations in a one-dimensional discrete-state stochastic model. It is explicitly analyzed using the first-passage time probabilities method to obtain a full dynamic description of the search process. A general dynamic phase diagram is developed. It is found that there are several dynamic regimes in the molecular search with conformational transitions, and they are determined by the relative values of the relevant length scales in the system. Theoretical predictions are fully supported by Monte Carlo computer simulations.

cond-mat.stat-mech↗

arXiv2017

Elasticity-based polymer sorting in active fluids: A Brownian dynamics study

While the dynamics of polymer chains in equilibrium media is well understood by now, the polymer dynamics in active non-equilibrium environments can be very different. Here we study the dynamics of polymers in a viscous medium containing self-propelled particles in two dimensions by using Brownian dynamics simulations. We find that the polymer center of mass exhibits a superdiffusive motion at short to intermediate times and the motion turns normal at long times, but with a greatly enhanced diffusivity. Interestingly, the long time diffusivity shows a non-monotonic behavior as a function of the chain length and stiffness. We analyze how the polymer conformation and the accumulation of the self-propelled particles, and therefore the directed motion of the polymer, are correlated. At the point of maximal polymer diffusivity, the polymer has preferentially bent conformations maintained by the balance between the chain elasticity and the propelling force generated by the active particles. We also consider the barrier crossing dynamics of actively-driven polymers in a double-well potential. The barrier crossing times are demonstrated to have a peculiar non-monotonic dependence, related to that of the diffusivity. This effect can be potentially utilized for sorting of polymers from solutions in \textit{in vitro} experiments.

cond-mat.soft↗

arXiv2015

Self-subdiffusion in solutions of star-shaped crowders: non-monotonic effects of inter-particle interactions

We examine by extensive computer simulations the self-diffusion of anisotropic star like particles in crowded two-dimensional solutions. We investigate the implications of the area coverage fraction $ϕ$ of the crowders and the crowder-crowder adhesion properties on the regime of transient anomalous diffusion. We systematically compute the mean squared displacement (MSD) of the particles, their time averaged MSD, as well as the effective diffusion coefficient. The diffusion appears ergodic in the limit of long traces, such that the time averaged MSD converges towards the ensemble averaged MSD and features a small residual amplitude spread of the time averaged MSD from individual trajectories. At intermediate time scales we quantify the anomalous diffusion in the system. Also, we show that the translational---but not rotational---diffusivity of the particles $D$ is a non-monotonic function of the attraction strength between them. Both diffusion coefficients decrease as $D(ϕ)\sim (1-ϕ/ϕ^*)^2$ with the area fraction $ϕ$ occupied by the crowders. Our results might be applicable to rationalising the experimental observations of non-Brownian diffusion for a number of standard macromolecular crowders used in vitro to mimic the cytoplasmic conditions of living cells.

cond-mat.soft↗

arXiv2014

Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size

The looping of polymers such as DNA is a fundamental process in the molecular biology of living cells, whose interior is characterised by a high degree of molecular crowding. We here investigate in detail the looping dynamics of flexible polymer chains in the presence of different degrees of crowding. From the analysis of the looping-unlooping rates and the looping probabilities of the chain ends we show that the presence of small crowders typically slow down the chain dynamics but larger crowders may in fact facilitate the looping. We rationalise these non-trivial and often counterintuitive effects of the crowder size onto the looping kinetics in terms of an effective solution viscosity and standard excluded volume effects. Thus for small crowders the effect of an increased viscosity dominates, while for big crowders we argue that confinement effects (caging) prevail. The tradeoff between both trends can thus result in the impediment or facilitation of polymer looping, depending on the crowder size. We also examine how the crowding volume fraction, chain length, and the attraction strength of the contact groups of the polymer chain affect the looping kinetics and hairpin formation dynamics. Our results are relevant for DNA looping in the absence and presence of protein mediation, DNA hairpin formation, RNA folding, and the folding of polypeptide chains under biologically relevant high-crowding conditions.

cond-mat.soft↗

arXiv2014

Mixing and segregation of ring polymers: spatial confinement and molecular crowding effects

During the life cycle of bacterial cells the non-mixing of the two ring-shaped daughter genomes is an important prerequisite for the cell division process. Mimicking the environments inside highly crowded biological cells, we study the dynamics and statistical behaviour of two flexible ring polymers in the presence of cylindrical confinement and crowding molecules. From extensive computer simulations we determine the degree of ring-ring overlap and the number of inter-monomer contacts for varying volume fractions $ϕ$ of crowders. We also examine the entropic de-mixing of polymer rings in the presence of mobile crowders and determine the characteristic times of the internal polymer dynamics. Effects of the ring length on ring-ring overlap are also analysed. In particular, on systematic variation of the fraction of crowding molecules a $(1-ϕ)$-scaling is found for the ring-ring overlap length along the cylinder axis, and a non-monotonic dependence of the 3D ring-ring contact number is predicted. Our results help to rationalise the implications of macromolecular crowding for circular DNA molecules in confined spaces inside bacteria as well as in localised cellular compartments inside eukaryotic cells.

cond-mat.soft↗

arXiv2013

Polymer Escape from a Metastable Kramers potential: Path Integral Hyperdynamics Study

We study the dynamics of flexible, semiflexible, and self-avoiding polymer chains moving under a Kramers metastable potential. Due to thermal noise, the polymers, initially placed in the metastable well, can cross the potential barrier, but these events are extremely rare if the barrier is much larger than thermal energy. To speed up the slow rate processes in computer simulations, we extend the recently proposed path integral hyperdynamics method to the cases of polymers. We consider the cases where the polymers' radii of gyration are comparable to the distance between the well bottom and the barrier top. We find that, for a flexible polymer, the crossing rate ($\mathcal{R}$) monotonically decreases with chain contour length ($L$), but with the magnitude much larger than the Kramers rate in the globular limit. For a semiflexible polymer, the crossing rate decreases with $L$ but becomes nearly constant for large $L$. For a fixed $L$, the crossing rate becomes maximum at an intermediate bending stiffness. For a self-avoiding chain, the rate is a nonmonotonic function of $L$, first decreasing with $L$, and then, above certain length, increasing with $L$. These findings can be instrumental for efficient separation of biopolymers.

cond-mat.soft↗

arXiv2013

Sensing viruses by mechanical tension of DNA in responsive hydrogels

The rapid worldwide spread of severe viral infections, often involving novel modifications of viruses, poses major challenges to our health care systems. This means that tools that can efficiently and specifically diagnose viruses are much needed. To be relevant for a broad application in local health care centers, such tools should be relatively cheap and easy to use. Here we discuss the biophysical potential for the macroscopic detection of viruses based on the induction of a mechanical stress in a bundle of pre-stretched DNA molecules upon binding of viruses to the DNA. We show that the affinity of the DNA to the charged virus surface induces a local melting of the double-helix into two single-stranded DNA. This process effects a mechanical stress along the DNA chains leading to an overall contraction of the DNA. Our results suggest that when such DNA bundles are incorporated in a supporting matrix such as a responsive hydrogel, the presence of viruses may indeed lead to a significant, macroscopic mechanical deformation of the matrix. We discuss the biophysical basis for this effect and characterize the physical properties of the associated DNA melting transition. In particular, we reveal several scaling relations between the relevant physical parameters of the system. We promote this DNA-based assay for efficient and specific virus screening.

q-bio.BM↗

arXiv2012

Polymer translocation under time-dependent driving forces: resonant activation induced by attractive polymer-pore interactions

We study the driven translocation of polymers under time-dependent driving forces using $N$-particle Langevin dynamics simulations. We consider the force to be either sinusoidally oscillating in time or dichotomic noise with exponential correlation time, to mimic both plausible experimental setups and naturally occurring biological conditions. In addition, we consider both the case of purely repulsive polymer-pore interactions and the case with additional attractive polymer-pore interactions, typically occurring inside biological pores. We find that the nature of the interaction fundamentally affects the translocation dynamics. For the non-attractive pore, the translocation time crosses over to a fast translocation regime as the frequency of the driving force decreases. In the attractive pore case, because of a free energy well induced inside the pore, the translocation time can be a minimum at the optimal frequency of the force, the so-called resonant activation. In the latter case, we examine the effect of various physical parameters on the resonant activation, and explain our observations using simple theoretical arguments.

cond-mat.soft↗

arXiv2011

Effects of static and temporally fluctuating tensions on semiflexible polymer looping

Biopolymer looping is a dynamic process that occurs ubiquitously in cells for gene regulation, protein folding, etc. In cellular environments, biopolymers are often subject to tensions which are either static, or temporally fluctuating far away from equilibrium. We study the dynamics of semiflexible polymer looping in the presence of such tensions by using Brownian dynamics simulation combined with an analytical theory. We show a minute tension dramatically changes the looping time, especially for long chains. Considering a dichotomically flipping noise as a simple example of the nonequilibrium tension, we find the phenomenon of resonant activation, where the looping time can be the minimum at an optimal flipping time. We discuss our results in connection with recent experiments.

cond-mat.soft↗