Biomedical subjects

Ralf Everaers

Publications and source records attributed to Ralf Everaers.

6 recordsLinked to original sources

PubMed2006

Indirect readout: detection of optimized subsequences and calculation of relative binding affinities using different DNA elastic potentials.

Essential biological processes require that proteins bind to a set of specific DNA sites with tuned relative affinities. We focus on the indirect readout mechanism and discuss its theoretical description in relation to the present understanding of DNA elasticity on the rigid base pair level. Combining existing parametrizations of elastic potentials for DNA, we derive elastic free energies directly related to competitive binding experiments, and propose a computationally inexpensive local marker for elastically optimized subsequences in protein-DNA co-crystals. We test our approach in an application to the bacteriophage 434 repressor. In agreement with known results we find that indirect readout dominates at the central, non-contacted bases of the binding site. Elastic optimization involves all deformation modes and is mainly due to the adapted equilibrium structure of the operator, while sequence-dependent elasticity plays a minor role. These qualitative observations are robust with respect to current parametrization uncertainties. Predictions for relative affinities mediated by indirect readout depend sensitively on the chosen parametrization. Their quantitative comparison with experimental data allows for a critical evaluation of DNA elastic potentials and of the correspondence between crystal and solution structures. The software written for the presented analysis is included as Supplementary Data.

Base Pairing↗

PubMed2004

Strain-dependent localization, microscopic deformations, and macroscopic normal tensions in model polymer networks.

We use molecular dynamics simulations to investigate the microscopic and macroscopic response of model polymer networks to uniaxial elongations. By studying networks with strand lengths ranging from N(s)=20 to 200 we cover the full crossover from cross-link to entanglement dominated behavior. Our results support a recent version of the tube model which accounts for the different strain dependence of chain localization due to chemical cross-links and entanglements.

Computer Simulation↗

PubMed2004

Nucleosome interactions in chromatin: fiber stiffening and hairpin formation.

We use Monte Carlo simulations to study attractive and excluded volume interactions between nucleosome core particles in 30-nm chromatin fibers. The nucleosomes are treated as disklike objects having an excluded volume and short-range attraction modeled by a variant of the Gay-Berne potential. The nucleosomes are connected via bendable and twistable linker DNA in the crossed linker fashion. We investigate the influence of the nucleosomal excluded volume on the stiffness of the fiber. For parameter values that correspond to chicken erythrocyte chromatin, we find that the persistence length is governed to a large extent by that excluded volume whereas the soft linker backbone elasticity plays only a minor role. We further find that internucleosomal attraction can induce the formation of hairpin configurations. Tension-induced opening of such configurations into straight fibers manifests itself in a quasiplateau in the force-extension curve that resembles results from recent micromanipulation experiments. Such hairpins may play a role in the formation of higher-order structures in chromosomes like chromonema fibers.

Chromatin↗

PubMed2004

Rheology and microscopic topology of entangled polymeric liquids.

The viscoelastic properties of high molecular weight polymeric liquids are dominated by topological constraints on a molecular scale. In a manner similar to that of entangled ropes, polymer chains can slide past but not through each other. Tube models of polymer dynamics and rheology are based on the idea that entanglements confine a chain to small fluctuations around a primitive path that follows the coarse-grained chain contour. Here we provide a microscopic foundation for these highly successful phenomenological models. We analyze the topological state of polymeric liquids in terms of primitive paths and obtain parameter-free, quantitative predictions for the plateau modulus, which agree with experiment for all major classes of synthetic polymers.

Journal Article↗

PubMed2003

Modeling DNA structure, elasticity, and deformations at the base-pair level.

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between the neighboring base pairs. The sugar-phosphate backbones are taken into account by semirigid harmonic springs with a nonzero spring length. The competition between these two interactions and the introduction of a simple geometrical constraint lead to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the stack-of-plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean-squared base-pair step parameters. For the optimized model parameters, we measured the critical force where the transition from B- to S-DNA occurs to be approximately 140 pN. We observe an overstretched S-DNA conformation with highly inclined bases which partially preserves the stacking of successive base pairs.

Base Composition↗

PubMed2002

Statistical mechanics of triangulated ribbons.

We use computer simulations and scaling arguments to investigate statistical and structural properties of a semiflexible ribbon composed of isosceles triangles. We study two different models, one where the bending energy is calculated from the angles between the normal vectors of adjacent triangles, the second where the edges are viewed as semiflexible polymers so that the bending energy is related to the angles between the tangent vectors of next-nearest-neighbor triangles. The first model can be solved exactly whereas the second is more involved. It was recently introduced by Liverpool and Golestanian, Phys. Rev. Lett. 80, 405 (1998); Phys. Rev. E 62, 5488 (2000) as a model for double-stranded biopolymers such as DNA. Comparing observables such as the autocorrelation functions of the tangent vectors and the bond-director field, the probability distribution functions of the end-to-end distance, and the mean-squared twist we confirm the existence of local twist correlation, but find no indications for other predicted features such as twist-stretch coupling, kinks, or oscillations in the autocorrelation function of the bond-director field.

Biomechanical Phenomena↗