Loop Exponent Research Articles

Disorder and denaturation transition in the generalized Poland–Scheraga model

We investigate the generalized Poland-Scheraga model, which is used in the bio-physical literature to model the DNA denaturation transition, in the case where the two strands are allowed to be non-complementary (and to have different lengths). The homogeneous model was recently studied from a mathematical point of view in [35, 7], via a 2-dimensional renewal approach, with a loop exponent 2+α (α > 0): it was found to undergo a localization/delocalization phase transition of order ν = min(1, α) −1 , together with – in general – other phase transitions. In this paper, we turn to the disordered model, and we address the question of the influence of disorder on the denaturation phase transition, that is whether adding an arbitrarily small amount of disorder (i.e. inhomogeneities) affects the critical properties of this transition. Our results are consistent with Harris' predictions for d-dimensional disordered systems (here d = 2). First, we prove that when α d/2), then disorder is irrelevant: the quenched and annealed critical points are equal, and the disordered denaturation phase transition is also of order ν = α −1. On the other hand, when α > 1, disorder is relevant: we prove that the quenched and annealed critical points differ. Moreover, we discuss a number of open problems, in particular the smoothing phenomenon that is expected to enter the game when disorder is relevant.

Cold denaturation of RNA secondary structures with loop entropy and quenched disorder.

The critical behavior of ribonucleic acid (RNA) secondary structures with quenched sequence randomness is studied by means of the constrained annealing method. A thermodynamic phase transition is induced by including the conformational weight of loop structures. In addition to the expected melting at high temperature, a cold-melting transition appears when the disorder strength induces competition between favorable and unfavorable base pairs. Our results suggest that the cold denaturation of RNA found experimentally might be triggered by quenched sequence disorder. We calculate hot- and cold-melting critical temperatures for competing favorable and unfavorable base-pair energies and present a folding phase diagram as a function of the loop exponent and temperature.

The random pinning model with correlated disorder given by a renewal set

We investigate the effect of correlated disorder on the localization transition undergone by a renewal sequence with loop exponent $\alpha$ > 0, when the correlated sequence is given by another independent renewal set with loop exponent $\alpha$ > 0. Using the renewal structure of the disorder sequence, we compute the annealed critical point and exponent. Then, using a smoothing inequality for the quenched free energy and second moment estimates for the quenched partition function, combined with decoupling inequalities, we prove that in the case $\alpha$ > 2 (summable correlations), disorder is irrelevant if $\alpha$ < 1/2 and relevant if $\alpha$ > 1/2, which extends the Harris criterion for independent disorder. The case $\alpha$ $\in$ (1, 2) (non-summable correlations) remains largely open, but we are able to prove that disorder is relevant for $\alpha$ > 1/ $\alpha$, a condition that is expected to be non-optimal. Predictions on the criterion for disorder relevance in this case are discussed. Finally, the case $\alpha$ $\in$ (0, 1) is somewhat special but treated for completeness: in this case, disorder has no effect on the quenched free energy, but the annealed model exhibits a phase transition.

Loop exponent in DNA bubble dynamics

Dynamics of DNA bubbles are of interest for both statistical physics and biology. We present exact solutions to the Fokker–Planck equation governing bubble dynamics in the presence of a long-range entropic interaction. The complete meeting time and meeting position probability distributions are derived from the solutions. Probability distribution functions (PDFs) reflect the value of the loop exponent of the entropic interaction. Our results extend previous results which concentrated mainly on the tails of the PDFs and open a way to determining the strength of the entropic interaction experimentally which has been a matter of recent discussions. Using numerical integration, we also discuss the influence of the finite size of a DNA chain on the bubble dynamics. Analogous results are obtained also for the case of subdiffusive dynamics of a DNA bubble in a heteropolymer, revealing highly universal asymptotics of meeting time and position probability functions.

Denaturation of circular DNA: Supercoils and overtwist

The denaturation transition of circular DNA is studied within a Poland-Scheraga-type approach, generalized to account for the fact that the total linking number (LK), which measures the number of windings of one strand around the other, is conserved. In the model the LK conservation is maintained by invoking both overtwisting and writhing (supercoiling) mechanisms. This generalizes previous studies, which considered each mechanism separately. The phase diagram of the model is analyzed as a function of the temperature and the elastic constant κ associated with the overtwisting energy for any given loop entropy exponent c. As in the case where the two mechanisms apply separately, the model exhibits no denaturation transition for c ≤ 2. For c > 2 and κ = 0 we find that the model exhibits a first-order transition. The transition becomes of higher order for any κ > 0. We also calculate the contribution of the two mechanisms separately in maintaining the conservation of the linking number and find that it is weakly dependent on the loop exponent c.

The [formula omitted] loop model on a three-dimensional lattice

We study a class of loop models, parameterized by a continuously varying loop fugacity n, on the hydrogen peroxide lattice, which is a three-dimensional cubic lattice of coordination number 3. For integer n>0, these loop models provide graphical representations for n-vector models on the same lattice, while for n=0 they reduce to the self-avoiding walk problem. We use worm algorithms to perform Monte Carlo studies of the loop model for n=0, 0.5, 1, 1.5, 2, 3, 4, 5 and 10 and obtain the critical points and a number of critical exponents, including the thermal exponent yt, magnetic exponent yh, and loop exponent yl. For integer n, the estimated values of yt and yh are found to agree with existing estimates for the three-dimensional O(n) universality class. The efficiency of the worm algorithms is reflected by the small value of the dynamic exponent z, determined from our analysis of the integrated autocorrelation times.

Denaturation of circular DNA: Supercoil mechanism

The denaturation transition which takes place in circular DNA is analyzed by extending the Poland-Scheraga (PS) model to include the winding degrees of freedom. We consider the case of a homopolymer whereby the winding number of the double-stranded helix, released by a loop denaturation, is absorbed by supercoils. We find that as in the case of linear DNA, the order of the transition is determined by the loop exponent c. However the first-order transition displayed by the PS model for c>2 in linear DNA is replaced by a continuous transition with arbitrarily high order as c approaches 2, while the second-order transition found in the linear case in the regime 1<c≤2 disappears. In addition, our analysis reveals that melting under fixed linking number is a condensation transition, where the condensate is a macroscopic loop which appears above the critical temperature.

Secondary structure formation of homopolymeric single-stranded nucleic acids including force and loop entropy: Implications for DNA hybridization

Loops are essential secondary structure elements in folded DNA and RNA molecules and proliferate close to the melting transition. Using a theory for nucleic acid secondary structures that accounts for the logarithmic entropy -c ln m for a loop of length m, we study homopolymeric single-stranded nucleic acid chains under external force and varying temperature. In the thermodynamic limit of a long strand, the chain displays a phase transition between a low-temperature/low-force compact (folded) structure and a high-temperature/high-force molten (unfolded) structure. The influence of c on phase diagrams, critical exponents, melting, and force extension curves is derived analytically. For vanishing pulling force, only for the limited range of loop exponents 2 < c ≲ 2.479 a melting transition is possible; for c ≤ 2 the chain is always in the folded phase and for 2.479 ≲ c always in the unfolded phase. A force-induced melting transition with singular behavior is possible for all loop exponents c < 2.479 and can be observed experimentally by single-molecule force spectroscopy. These findings have implications for the hybridization or denaturation of double-stranded nucleic acids. The Poland-Scheraga model for nucleic acid duplex melting does not allow base pairing between nucleotides on the same strand in denatured regions of the double strand. If the sequence allows these intra-strand base pairs, we show that for a realistic loop exponent c ≈ 2.1 pronounced secondary structures appear inside the single strands. This leads to a lower melting temperature of the duplex than predicted by the Poland-Scheraga model. Further, these secondary structures renormalize the effective loop exponent [Formula: see text], which characterizes the weight of a denatured region of the double strand, and thus affect universal aspects of the duplex melting transition.

Theory for RNA Folding, Stretching, and Melting Including Loops and Salt

Secondary structure formation of nucleic acids strongly depends on salt concentration and temperature. We develop a theory for RNA folding that correctly accounts for sequence effects, the entropic contributions associated with loop formation, and salt effects. Using an iterative expression for the partition function that neglects pseudoknots, we calculate folding free energies and minimum free energy configurations based on the experimentally derived basepairing free energies. The configurational entropy of loop formation is modeled by the asymptotic expression −clnm, where m is the length of the loop and c the loop exponent, which is an adjustable constant. Salt effects enter in two ways: first, we derive salt-induced modifications of the free energy parameters for describing basepairing, and second, we include the electrostatic free energy for loop formation. Both effects are modeled on the Debye-Hückel level including counterion condensation. We validate our theory for two different RNA sequences. For tRNA-phe, the resultant heat capacity curves for thermal denaturation at various salt concentrations accurately reproduce experimental results. For the P5ab RNA hairpin, we derive the global phase diagram in the three-dimensional space spanned by temperature, stretching force, and salt concentration and obtain good agreement with the experimentally determined critical unfolding force. We show that for a proper description of RNA melting and stretching, both salt and loop entropy effects are needed.

A Three-State Model with Loop Entropy for the Overstretching Transition of DNA

We introduce a three-state model for a single DNA chain under tension that distinguishes among B-DNA, S-DNA, and M (molten or denatured) segments and at the same time correctly accounts for the entropy of molten loops, characterized by the exponent c in the asymptotic expression S ∼ –c ln n for the entropy of a loop of length n. Force extension curves are derived exactly by employing a generalized Poland-Scheraga approach and then compared to experimental data. Simultaneous fitting to force-extension data at room temperature and to the denaturation phase transition at zero force is possible and allows us to establish a global phase diagram in the force-temperature plane. Under a stretching force, the effects of the stacking energy (entering as a domain-wall energy between paired and unpaired bases) and the loop entropy are separated. Therefore, we can estimate the loop exponent c independently from the precise value of the stacking energy. The fitted value for c is small, suggesting that nicks dominate the experimental force extension traces of natural DNA.

Equality of critical points for polymer depinning transitions with loop exponent one

We consider a polymer with configuration modelled by the trajectory of a Markov chain, interacting with a potential of form $u+V_n$ when it visits a particular state 0 at time $n$, with $\{V_n\}$ representing i.i.d. quenched disorder. There is a critical value of $u$ above which the polymer is pinned by the potential. A particular case not covered in a number of previous studies is that of loop exponent one, in which the probability of an excursion of length $n$ takes the form $\phi(n)/n$ for some slowly varying $\phi$; this includes simple random walk in two dimensions. We show that in this case, at all temperatures, the critical values of $u$ in the quenched and annealed models are equal, in contrast to all other loop exponents, for which these critical values are known to differ, at least at low temperatures.

DNA unzipping phase diagram calculated via replica theory

We show how single-molecule unzipping experiments can provide strong evidence that the zero-force melting transition of long molecules of natural dsDNA should be classified as a phase transition of the higher-order type (continuous). Toward this end, we study a statistical-mechanics model for the fluctuating structure of a long molecule of dsDNA, and compute the equilibrium phase diagram for the experiment in which the molecule is unzipped under applied force. We consider a perfect-matching dsDNA model, in which the loops are volume-excluding chains with arbitrary loop exponent c . We include stacking interactions, hydrogen bonds, and main-chain entropy. We include sequence heterogeneity at the level of random sequences; in particular, there is no correlation in the base-pairing (bp) energy from one sequence position to the next. We present heuristic arguments to demonstrate that the low-temperature macrostate does not exhibit degenerate ergodicity breaking. We use this claim to understand the results of our replica-theoretic calculation of the equilibrium properties of the system. As a function of temperature, we obtain the minimal force at which the molecule separates completely. This critical-force curve is a line in the temperature-force phase diagram that marks the regions where the molecule exists primarily as a double helix versus the region where the molecule exists as two separate strands. We compare our random-sequence model to magnetic tweezer experiments performed on the 48 502 bp genome of bacteriophage lambda . We find good agreement with the experimental data, which is restricted to temperatures between 24 and 50 degrees C . At higher temperatures, the critical-force curve of our random-sequence model is very different for that of the homogeneous-sequence version of our model. For both sequence models, the critical force falls to zero at the melting temperature T_{c} like |T-T_{c}|;{alpha} . For the homogeneous-sequence model, alpha=1/2 almost exactly, while for the random-sequence model, alpha approximately 0.9 . Importantly, the shape of the critical-force curve is connected, via our theory, to the manner in which the helix fraction falls to zero at T_{c} . The helix fraction is the property that is used to classify the melting transition as a type of phase transition. In our calculation, the shape of the critical-force curve holds strong evidence that the zero-force melting transition of long natural dsDNA should be classified as a higher-order (continuous) phase transition. Specifically, the order is 3rd or greater.

Forced-Induced Desorption of a Polymer Chain Adsorbed on an Attractive Surface: Theory and Computer Experiment

We consider the properties of a self-avoiding polymer chain adsorbed on a solid attractive substrate which is attached with one end to a pulling force. The conformational properties of such chain and its phase behavior are treated within a grand canonical ensemble (GCE) approach. We derive theoretical expressions for the mean size of loops, trains, and tails of an adsorbed chain under pulling as well as values for the universal exponents which describe their probability distribution functions. A central result of the theoretical analysis is the derivation of an expression for the crossover exponent ϕ, characterizing polymer adsorption at criticality, ϕ = α — 1, which relates the precise value of ϕ to the exponent α, describing polymer loop statistics. We demonstrate that 1 — γ11 < α < 1 + ν, depending on the possibility of a single loop to interact with neighboring loops in the adsorbed polymer. The universal surface loop exponent γ11 ≈ −0.39 and the Flory exponent ν ≈ 0.59. We present the adsorption−desorption phase diagram of a polymer chain under pulling and demonstrate that the relevant phase transformation becomes first order whereas in the absence of external force it is known to be a continuous one. The nature of this transformation turns to be dichotomic; i.e., coexistence of different phase states is not possible. These novel theoretical predictions are verified by means of extensive Monte Carlo simulations.

Disordered pinning models and copolymers: Beyond annealed bounds

We consider a general model of a disordered copolymer with adsorption. This includes, as particular cases, a generalization of the copolymer at a selective interface introduced by Garel et al. [Europhys. Lett. 8 (1989) 9–13], pinning and wetting models in various dimensions, and the Poland–Scheraga model of DNA denaturation. We prove a new variational upper bound for the free energy via an estimation of noninteger moments of the partition function. As an application, we show that for strong disorder the quenched critical point differs from the annealed one, for example, if the disorder distribution is Gaussian. In particular, for pinning models with loop exponent 0<α<1/2 this implies the existence of a transition from weak to strong disorder. For the copolymer model, under a (restrictive) condition on the law of the underlying renewal, we show that the critical point coincides with the one predicted via renormalization group arguments in the theoretical physics literature. A stronger result holds for a “reduced wetting model” introduced by Bodineau and Giacomin [J. Statist. Phys. 117 (2004) 801–818]: without restrictions on the law of the underlying renewal, the critical point coincides with the corresponding renormalization group prediction.

Denaturation Transition of Stretched DNA

We generalize the Poland-Scheraga model to consider DNA denaturation in the presence of an external stretching force. We demonstrate the existence of a force-induced DNA denaturation transition and obtain the temperature-force phase diagram. The transition is determined by the loop exponent c, for which we find the new value c = 4 nu-1/2 such that the transition is second order with c = 1.85 < 2 in d = 3. We show that a finite stretching force F destabilizes DNA, corresponding to a lower melting temperature T(F), in agreement with single-molecule DNA stretching experiments.

Loop Dynamics in DNA Denaturation

The dynamics of a loop in DNA molecules at the denaturation transition is studied by scaling arguments and numerical simulations. The autocorrelation function of the state of complementary bases (either closed or open) is calculated. The long-time decay of the autocorrelation function is expressed in terms of the loop exponent c both for homopolymers and heteropolymers. This suggests an experimental method for measuring the exponent c using florescence correlation spectroscopy.

Scale-free network hidden in a collapsing polymer

We show that the collapsed globular phase of a polymer accommodates a scale-free incompatibility graph of its contacts. The degree distribution of this network is found to decay with the exponent gamma=1/(2-c) up to a cutoff degree dc proportional to L(2-c), where is the loop exponent for dense polymers (c=11/8 in two dimensions) and is the length of the polymer. Our results exemplify how a scale-free network can emerge from standard criticality.

Reparametrizing the loop entropy weights: effect on DNA melting curves.

Recent advances in the understanding of the melting behavior of double-stranded DNA with statistical mechanics methods lead to improved estimates of the weight factors for the dissociation events of the chains, in particular for interior loop melting. So far, in the modeling of DNA melting, the entropy of denaturated loops has been estimated from the number of configurations of a closed self-avoiding walk. It is well understood now that a loop embedded in a chain is characterized by a loop closure exponent c which is higher than that of an isolated loop. Here we report an analysis of DNA melting curves for sequences of a broad range of lengths (from 10 to 10(6) base pairs) calculated with a program based on the algorithms underlying MELTSIM. Using the embedded loop exponent we find that the cooperativity parameter is one order of magnitude bigger than current estimates. We argue that in the melting region the double helix persistence length is greatly reduced compared to its room temperature value, so that the use of the embedded loop closure exponent for real DNA sequences is justified.

Thermal stability of DNA.

Tij and Delta Hij for stacking of pair i upon j in DNA have been obtained over the range 0.034-0.114 M Na+from high-resolution melting curves of well-behaved synthetic tandemly repeating inserts in recombinant pN/MCS plasmids. Results are consistent with neighbor-pair thermodynamic additivity, where the stability constant, sij , for different domains of length N depend quantitatively on the product of stability constants for each individual pair in domains, sijN . Unit transition enthalpies with average errors less than +/-5%, were determined by analysis of two-state equilibria associated with the melting of internal domains and verified from variations of Tij with [Na+]. Enthalpies increase with Tij , in close agreement with the empirical function: Delta Hij = 52.78@ Tij - 9489, and in parallel with a smaller increase in Delta Sij . Delta Hij and Delta Sij are in good agreement with the results of an extensive compilation of published Delta Hcal and Delta Scal for synthetic and natural DNAs. Neighbor-pair additivity was also observed for (dA@dT)-tracts at melting temperatures; no evidence could be detected of the familiar and unusual structural features that characterize tracts at lower temperatures. The energetic effects of loops were determined from the melting behavior of repeating inserts installed between (G+C)-rich barrier domains in the pN/MCS plasmids. A unique set of values for the cooperativity, loop exponent and stiffness parameters were found applicable to internal domains of all sizes and sequences. Statistical mechanical curves calculated with values of Tij([Na+]) , Delta Hij and these loop parameters are in good agreement with observation.