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At least 1,279 records · Page 71Linked to original sources

Structural Determinant of Protein Designability

Here we present an approximate analytical theory for the relationship between a protein structure's contact matrix and the shape of its energy spectrum in amino acid sequence space. We demonstrate a dependence of the number of sequences of low energy in a structure on the eigenvalues of the structure's contact matrix, and then use a Monte Carlo simulation to test the applicability of this analytical result to cubic lattice proteins. We find that the lattice structures with the most low-energy sequences are the same as those predicted by the theory. We argue that, given sufficiently strict requirements for foldability, these structures are the most designable, and we propose a simple means to test whether the results in this paper hold true for real proteins.

cond-mat.soft↗

Unzipping Kinetics of Double-Stranded DNA in a Nanopore

We studied the unzipping kinetics of single molecules of double-stranded DNA by pulling one of their two strands through a narrow protein pore. PCR analysis yielded the first direct proof of DNA unzipping in such a system. The time to unzip each molecule was inferred from the ionic current signature of DNA traversal. The distribution of times to unzip under various experimental conditions fit a simple kinetic model. Using this model, we estimated the enthalpy barriers to unzipping and the effective charge of a nucleotide in the pore, which was considerably smaller than previously assumed.

cond-mat.soft↗

Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum Gō models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kinetic trapping caused by some of the folding intermediates' nonnative topologies. Notably, simple two-state folding kinetics of small single-domain proteins are not reproduced by common Gō-like schemes.

cond-mat.soft↗

Particle Dispersion on Rapidly Folding Random Hetero-Polymers

We investigate the dynamics of a particle moving randomly along a disordered hetero-polymer subjected to rapid conformational changes which induce superdiffusive motion in chemical coordinates. We study the antagonistic interplay between the enhanced diffusion and the quenched disorder. The dispersion speed exhibits universal behavior independent of the folding statistics. On the other hand it is strongly affected by the structure of the disordered potential. The results may serve as a reference point for a number of translocation phenomena observed in biological cells, such as protein dynamics on DNA strands.

cond-mat.stat-mech↗

Synchronization of active mechanical oscillators by an inertial load

Motivated by the operation of myogenic (self-oscillatory) insect flight muscle, we study a model consisting of a large number of identical oscillatory contractile elements joined in a chain, whose end is attached to a damped mass-spring oscillator. When the inertial load is small, the serial coupling favors an antisynchronous state in which the extension of one oscillator is compensated by the contraction of another, in order to preserve the total length. However, a sufficiently massive load can sychronize the oscillators and can even induce oscillation in situations where isolated elements would be stable. The system has a complex phase diagram displaying quiescent, synchronous and antisynchrononous phases, as well as an unsual asynchronous phase in which the total length of the chain oscillates at a different frequency from the individual active elements.

physics.bio-ph↗

A possible mechanism for cold denaturation of proteins at high pressure

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.

cond-mat.soft↗

Equilibrium Distribution of Mutators in the Single Fitness Peak Model

This paper develops an analytically tractable model for determining the equilibrium distribution of mismatch repair deficient strains in unicellular populations. The approach is based on the single fitness peak (SFP) model, which has been used in Eigen's quasispecies equations in order to understand various aspects of evolutionary dynamics. As with the quasispecies model, our model for mutator-nonmutator equilibrium undergoes a phase transition in the limit of infinite sequence length. This "repair catastrophe" occurs at a critical repair error probability of $ ε_r = L_{via}/L $, where $ L_{via} $ denotes the length of the genome controlling viability, while $ L $ denotes the overall length of the genome. The repair catastrophe therefore occurs when the repair error probability exceeds the fraction of deleterious mutations. Our model also gives a quantitative estimate for the equilibrium fraction of mutators in {\it Escherichia coli}.

cond-mat.stat-mech↗

Chromatin dynamics: Nucleosomes go mobile through twist defects

We study the spontaneous ''sliding'' of histone spools (nucleosomes) along DNA as a result of thermally activated single base pair twist defects. To this end we map the system onto a suitably extended Frenkel-Kontorova model. Combining results from several recent experiments we are able to estimate the nucleosome mobility without adjustable parameters. Our model shows also how the local mobility is intimately linked to the underlying base pair sequence.

cond-mat.soft↗

Non-local Interaction Effects on Pattern Formation in Population Dynamics

We consider a model for population dynamics such as for the evolution of bacterial colonies which is of the Fisher type but where the competitive interaction among individuals is non-local, and show that spatial structures with interesting features emerge. These features depend on the nature of the competitive interaction as well as on its range, specifically on the presence or absence of tails in, and the central curvature of, the influence function of the interaction.

nlin.PS↗

RNA denaturation: excluded volume, pseudoknots and transition scenarios

A lattice model of RNA denaturation which fully accounts for the excluded volume effects among nucleotides is proposed. A numerical study shows that interactions forming pseudoknots must be included in order to get a sharp continuous transition. Otherwise a smooth crossover occurs from the swollen linear polymer behavior to highly ramified, almost compact conformations with secondary structures. In the latter scenario, which is appropriate when these structures are much more stable than pseudoknot links, probability distributions for the lengths of both loops and main branches obey scaling with nonclassical exponents.

cond-mat.soft↗

An Effective Membrane Model of the Immunological Synapse

The immunological synapse is a patterned collection of different types of receptors and ligands that forms in the intercellular junction between T Cells and antigen presenting cells (APCs) during recognition. The synapse is implicated in information transfer between cells, and is characterized by different spatial patterns of receptors at different stages in the life cycle of T cells. We obtain a minimalist model that captures this experimentally observed phenomenology. A functional RG analysis provides further insights.

cond-mat.soft↗

Multicanonical Chain Growth Algorithm

We present a temperature-independent Monte Carlo method for the determination of the density of states of lattice proteins that combines the fast ground-state search strategy of the nPERM chain growth and multicanonical reweighting for sampling the complete energy space. Since the density of states contains all energetic information of a statistical system, we can directly calculate the mean energy, specific heat, Gibbs free energy, and entropy for all temperatures. We apply this method to HP lattice proteins and for the examples of sequences considered, we identify the transitions between native, globule, and random coil states. Since no special properties of heteropolymers are involved in this algorithm, the method applies to polymer models as well.

cond-mat.stat-mech↗

The internal states of active inclusions and the dynamics of an active membrane

A theoretical model of a two-component fluid membrane containing lipids and two-state active inclusions is presented. Under strong inclusion activities the membrane can be unstable due to pump-driven undulation or aggregation of high curvature excited inclusions. Depending on the structural details of the inclusions, the active conformation change of the inclusions can also induce finite size domains on the membrane. At long wavelengths a stable membrane has a height fluctuation spectrum similar to previous studies which neglected the inclusion internal states. For a tensionless membrane, $ \sim T_{eff} q_{\perp}^{-4}$, where $T_{eff}$ is an effective temperature which depends on the details of inclusion activities.

cond-mat.soft↗

DNA Spools under Tension

DNA-spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core are ubiquitous in nature. We develop a general theory describing the non-equilibrium behavior of DNA-spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics.

cond-mat.soft↗

Internal Motility in Stiffening Actin-Myosin Networks

We present a study on filamentous actin solutions containing heavy meromyosin subfragments of myosin II motor molecules. We focus on the viscoelastic phase behavior and internal dynamics of such networks during ATP depletion. Upon simultaneously using micro-rheology and fluorescence microscopy as complementary experimental tools, we find a sol-gel transition accompanied by a sudden onset of directed filament motion. We interpret the sol-gel transition in terms of myosin II enzymology, and suggest a "zipping" mechanism to explain the filament motion in the vicinity of the sol-gel transition.

physics.bio-ph↗

From polymers to proteins -- novel phases of short compact tubes

A framework is presented for understanding the common character of proteins. Proteins are linear chain molecules. However, the simple model of a polymer viewed as spheres tethered together does not account for many of the observed characteristics of protein structures. The authors show here that proteins may be regarded as tubes of nonzero thickness. This approach allows one to bridge the conventional compact polymer phase with a novel phase employed by Nature to house biomolecular structures. The continuum description of a tube (or a sheet) of arbitrary thickness entails using appropriately chosen many-body interactions rather than two-body interactions. The authors suggest that the structures of folded proteins are selected based on geometrical considerations and are poised at the edge of compaction, thus accounting for their versatility and flexibility. This approach also offers an explanation for why helices and sheets are the building blocks of protein structures.

cond-mat.stat-mech↗

Effective Fitness Landscapes for Evolutionary Systems

In evolution theory the concept of a fitness landscape has played an important role, evolution itself being portrayed as a hill-climbing process on a rugged landscape. In this article it is shown that in general, in the presence of other genetic operators such as mutation and recombination, hill-climbing is the exception rather than the rule. This descrepency can be traced to the different ways that the concept of fitness appears --- as a measure of the number of fit offspring, or as a measure of the probability to reach reproductive age. Effective fitness models the former not the latter and gives an intuitive way to understand population dynamics as flows on an effective fitness landscape when genetic operators other than selection play an important role. The efficacy of the concept is shown using several simple analytic examples and also some more complicated cases illustrated by simulations.

nlin.AO↗

Jigsaw model of the origin of life

It is suggested that life originated in a three-step process referred to as the jigsaw model. RNA, proteins, or similar organic molecules polymerized in a dehydrated carbon-rich environment, on surfaces in a carbon-rich environment, or in another environment where polymerization occurs. These polymers subsequently entered an aqueous environment where they folded into compact structures. It is argued that the folding of randomly generated polymers such as RNA or proteins in water tends to partition the folded polymer into domains with hydrophobic cores and matching shapes to minimize energy. In the aqueous environment, hydrolysis or other reactions fragmented the compact structures into two or more matching molecules, occasionally producing simple living systems, also known as autocatalytic sets of molecules. It is argued that the hydrolysis of folded polymers such as RNA or proteins is not random. The hydrophobic cores of the domains are rarely bisected due to the energy requirements in water. Hydrolysis preferentially fragments the folded polymers into pieces with complementary structures and chemical affinities. Thus the probability of producing a system of matched, interacting molecules in prebiotic chemistry is much higher than usually estimated. Environments where this process may occur are identified. For example, the jigsaw model suggests life may have originated at a seep of carbonaceous fluids beneath the ocean. The polymerization occurred beneath the sea floor. The folding and fragmentation occurred in the ocean. The implications of this hypothesis for seeking life or prebiotic chemistry in the Solar System are explored.

nlin.AO↗