TY - JOUR A1 - Talukder, Srijeeta A1 - Sen, Shrabani A1 - Chakraborti, Prantik A1 - Metzler, Ralf A1 - Banik, Suman K. A1 - Chaudhury, Pinaki T1 - Breathing dynamics based parameter sensitivity analysis of hetero-polymeric DNA JF - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization. (c) 2014 AIP Publishing LLC. Y1 - 2014 U6 - https://doi.org/10.1063/1.4869112 SN - 0021-9606 SN - 1089-7690 VL - 140 IS - 12 PB - American Institute of Physics CY - Melville ER - TY - GEN A1 - Talukder, Srijeeta A1 - Sen, Shrabani A1 - Chakraborti, Prantik A1 - Metzler, Ralf A1 - Banik, Suman K. A1 - Chaudhury, Pinaki T1 - Breathing dynamics based parameter sensitivity analysis of hetero-polymeric DNA T2 - The journal of chemical physics : bridges a gap between journals of physics and journals of chemistr N2 - We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization. Y1 - 2014 U6 - https://doi.org/10.1063/1.4871297 SN - 0021-9606 SN - 1089-7690 VL - 140 IS - 14 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf ED - Metzler, Ralf T1 - Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size JF - Soft Matter N2 - 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 slows 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 on the looping kinetics in terms of an effective solution viscosity and standard excluded volume. It is shown that 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. KW - gene-regulation kinetics KW - physiological consequences KW - spatial-organization KW - anomalous diffusion KW - folding kinetics KW - living cells KW - dna coiling KW - in-vitro KW - dynamics KW - mixtures Y1 - 2014 SN - 1744-683X SP - 472 EP - 488 PB - The Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size N2 - 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 slows 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 on the looping kinetics in terms of an effective solution viscosity and standard excluded volume. It is shown that 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 185 KW - gene-regulation kinetics KW - physiological consequences KW - spatial-organization KW - anomalous diffusion KW - folding kinetics KW - living cells KW - dna coiling KW - in-vitro KW - dynamics KW - mixtures Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-76961 SP - 472 EP - 488 PB - The Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Mixing and segregation of ring polymers: spatial confinement and molecular crowding effects JF - New journal of physics : the open-access journal for physics N2 - 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 behavior 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 phi of crowders. We also examine the entropic demixing 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 analyzed. In particular, on systematic variation of the fraction of crowding molecules, a (1 - phi)-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 with a maximum at phi approximate to 0.2 is obtained. Our results demonstrate that polymer rings are demixed and separated by particular entropy-favourable partitioning of crowders along the axis of the cylindrical simulation box. These findings help to rationalize the implications of macromolecular crowding for circular DNA molecules in confined spaces inside bacteria as well as in localized cellular compartments inside eukaryotic cells. KW - polymers KW - confinement KW - crowding Y1 - 2014 U6 - https://doi.org/10.1088/1367-2630/16/5/053047 SN - 1367-2630 VL - 16 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Shin, Jaeoh A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Sensing viruses by mechanical tension of DNA in responsive hydrogels JF - Physical review : X, Expanding access N2 - The rapid worldwide spread of severe viral infections, often involving novel mutations 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 broad applications in local health-care centers, such tools should be relatively cheap and easy to use. In this paper, we discuss the biophysical potential for the macroscopic detection of viruses based on the induction of a mechanical stress in a bundle of prestretched 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 as a possible tool for efficient and specific virus screening. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevX.4.021002 SN - 2160-3308 VL - 4 IS - 2 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Schulz, Johannes H. P. A1 - Barkai, Eli A1 - Metzler, Ralf T1 - Aging renewal theory and application to random walks JF - Physical review : X, Expanding access N2 - We discuss a renewal process in which successive events are separated by scale-free waiting time periods. Among other ubiquitous long-time properties, this process exhibits aging: events counted initially in a time interval [0, t] statistically strongly differ from those observed at later times [t(a,) t(a) + t]. The versatility of renewal theory is owed to its abstract formulation. Renewals can be interpreted as steps of a random walk, switching events in two-state models, domain crossings of a random motion, etc. In complex, disordered media, processes with scale-free waiting times play a particularly prominent role. We set up a unified analytical foundation for such anomalous dynamics by discussing in detail the distribution of the aging renewal process. We analyze its half-discrete, half-continuous nature and study its aging time evolution. These results are readily used to discuss a scale-free anomalous diffusion process, the continuous-time random walk. By this, we not only shed light on the profound origins of its characteristic features, such as weak ergodicity breaking, along the way, we also add an extended discussion on aging effects. In particular, we find that the aging behavior of time and ensemble averages is conceptually very distinct, but their time scaling is identical at high ages. Finally, we show how more complex motion models are readily constructed on the basis of aging renewal dynamics. Y1 - 2014 U6 - https://doi.org/10.1103/PhysRevX.4.011028 SN - 2160-3308 VL - 4 IS - 1 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Sandev, Trifce A1 - Metzler, Ralf A1 - Tomovski, Zivorad T1 - Correlation functions for the fractional generalized Langevin equation in the presence of internal and external noise JF - Journal of mathematical physics N2 - We study generalized fractional Langevin equations in the presence of a harmonic potential. General expressions for the mean velocity and particle displacement, the mean squared displacement, position and velocity correlation functions, as well as normalized displacement correlation function are derived. We report exact results for the cases of internal and external friction, that is, when the driving noise is either internal and thus the fluctuation-dissipation relation is fulfilled or when the noise is external. The asymptotic behavior of the generalized stochastic oscillator is investigated, and the case of high viscous damping (overdamped limit) is considered. Additional behaviors of the normalized displacement correlation functions different from those for the regular damped harmonic oscillator are observed. In addition, the cases of a constant external force and the force free case are obtained. The validity of the generalized Einstein relation for this process is discussed. The considered fractional generalized Langevin equation may be used to model anomalous diffusive processes including single file-type diffusion. Y1 - 2014 U6 - https://doi.org/10.1063/1.4863478 SN - 0022-2488 SN - 1089-7658 VL - 55 IS - 2 PB - American Institute of Physics CY - Melville ER - TY - JOUR A1 - Sanders, Lloyd P. A1 - Lomholt, Michael A. A1 - Lizana, Ludvig A1 - Fogelmark, Karl A1 - Metzler, Ralf A1 - Ambjoernsson, Tobias T1 - Severe slowing-down and universality of the dynamics in disordered interacting many-body systems: ageing and ultraslow diffusion JF - New journal of physics : the open-access journal for physics N2 - Low-dimensional, many-body systems are often characterized by ultraslow dynamics. We study a labelled particle in a generic system of identical particles with hard-core interactions in a strongly disordered environment. The disorder is manifested through intermittent motion with scale-free sticking times at the single particle level. While for a non-interacting particle we find anomalous diffusion of the power-law form < x(2)(t)> similar or equal to t(alpha) of the mean squared displacement with 0 < alpha < 1, we demonstrate here that the combination of the disordered environment with the many-body interactions leads to an ultraslow, logarithmic dynamics < x(2)(t)> similar or equal to log(1/2)t with a universal 1/2 exponent. Even when a characteristic sticking time exists but the fluctuations of sticking times diverge we observe the mean squared displacement < x(2)(t)> similar or equal to t(gamma) with 0 < gamma < 1/2, that is slower than the famed Harris law < x(2)(t)> similar or equal to t(1/2) without disorder. We rationalize the results in terms of a subordination to a counting process, in which each transition is dominated by the forward waiting time of an ageing continuous time process. KW - single-file diffusion KW - continuous time random walks KW - ageing Y1 - 2014 U6 - https://doi.org/10.1088/1367-2630/16/11/113050 SN - 1367-2630 VL - 16 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Palyulin, Vladimir V. A1 - Metzler, Ralf T1 - Speeding up the first-passage for subdiffusion by introducing a finite potential barrier JF - Journal of physics : A, Mathematical and theoretical N2 - We show that for a subdiffusive continuous time random walk with scale-free waiting time distribution the first-passage dynamics on a finite interval can be optimized by introduction of a piecewise linear potential barrier. Analytical results for the survival probability and first-passage density based on the fractional Fokker-Planck equation are shown to agree well with Monte Carlo simulations results. As an application we discuss an improved design for efficient translocation of gradient copolymers compared to homopolymer translocation in a quasi-equilibrium approximation. KW - first passage KW - anomalous diffusion KW - potential landscape KW - polymer translocation Y1 - 2014 U6 - https://doi.org/10.1088/1751-8113/47/3/032002 SN - 1751-8113 SN - 1751-8121 VL - 47 IS - 3 PB - IOP Publ. Ltd. CY - Bristol ER -