Conformational transitions in single polymer molecules modeled with a complete energy landscape: continuous two-state model

An extension of the two-state Freely Jointed Chain model is presented in which the discrete energies of the two conformers are replaced by continuous functions of the conformer length. The statistical mechanics is initially developed in the Gibbs ensemble and leads to a conformational multi-state model. This is used to fit the equilibrium force-extension curve for Dextran. The continuous model also allows the use of Transfer Matrix methods to calculate all statistical properties in the Helmholtz ensemble, including thermal fluctuations. The latter are obtained with near perfect agreement to experiment.     

Essential dynamics and sidechain hydrogen bond cluster studies on eosinophil cationic protein

Eosinophil Cationic Protein (ECP) is a member of RNase A superfamily which carries out the obligatory catalytic role of cleaving RNA. It is involved in a variety of biological functions. Molecular dynamics simulations followed by essential dynamics analysis on this protein are carried out with the goal of gaining insights into the dynamical properties at atomic level. The top essential modes contribute to subspaces and to the transition phase. Further, the sidechain-sidechain/sidechain-mainchain hydrogen bond clusters are analyzed in the top modes, and compared with those of crystal structure. The role of residues identified by these methods is discussed in the context of concerted motion, structure and stability of the protein. Received 16 January 2002 Published online 13 September 2002     

Comparison of the measured phase diagrams in the force-temperature plane for the unzipping of two different natural DNA sequences

In this work, we consider the critical force required to unzip two different naturally occurring sequences of double-stranded DNA (dsDNA) at temperatures ranging from 20 ^°C to 50 ^°C, where one of the sequences has a 53% average guanine-cytosine (GC) content and the other has a 40% GC content. We demonstrate that the force required to separate the dsDNA of the 53% GC sequence into single-stranded DNA (ssDNA) is approximately 0.5 pN, or approximately 5% greater than the critical force required to unzip the 40% GC sequence at the same temperature. In the temperature range between 20 and 40 ^°C the measured critical forces correspond reasonably well to predictions based on a simple theoretical homopolymeric model, but at temperatures above 40 ^°C the measured critical forces are much smaller than the predicted forces. The correspondence between theory and experiment is not improved by using Monte Carlo simulations that consider the heteropolymeric nature of the sequences.     

DNA nucleotides: A case study of evolution

The evolution in coding DNA sequences brings new flexibility and freedom to the codon words, even as the underlying nucleotides get significantly ordered. These curious contra-rules of gene organisation are observed from the distribution of words and the second moments of the nucleotide letters. We apply these statistical data to determine the relative positions of a few bacterial groups as per their divergence in the geological timescale. Received 3 January 2002     

Osmotic force resisting chain insertion in a colloidal suspension

We consider the problem of inserting a stiff chain into a colloidal suspension of particles that interact with it through excluded volume forces. The free energy of insertion is associated with the work of creating a cavity devoid of colloid and sufficiently large to accommodate the chain. The corresponding work per unit length is the force that resists the entry of the chain into the colloidal suspension. In the case of a hard sphere fluid, this work can be calculated straightforwardly within the scaled particle theory; for solutions of flexible polymers, on the other hand, we employ simple scaling arguments. The forces computed in these ways are shown, for nanometer chain and colloid diameters, to be of the order of tens of pN for solution volume fractions of a few tenths. These magnitudes are argued to be important for biophysical processes such as the ejection of DNA from viral capsids into the cell cytoplasm. Received 18 December 2002 Published online: 16 April 2003 RID="a" ID="a"e-mail: castel@chem.ucla.edu RID="b" ID="b"Present address: Courant Institute of Mathematical Sciences, NYU, New York, New York 10012, USA     

Compressing a rigid filament: Buckling and cyclization

We study elastic properties of rigid filaments modeled as stiff chains shorter than their persistence length. By rigid filaments we mean that fluctuations around the optimal filament shape are weak and that low-order expansions (quadratic or quartic) in the deviation from the optimal shape are sufficient to describe them. Our main interest lies in the profiles of force vs. projected filament length, closure probability and weakly buckled states. Results may be relevant to experiments on self-assembled biological (microtubules, actin filaments) and synthetic (organo-gelators) filaments, carbon nanotubes and polymers grafted with strongly repelling side chains, some of which are discussed here.     

Correlation in a Gaussian chain with the ends fixed

We consider an ideal chain whose ends are fixed without fluctuation at different points, possibly by optical tweezers. We derive a two-point probability distribution of a corresponding random walk and explicitly calculate the scattering function. We find that the contour plot of the resulting function shows a kind of normal butterfly pattern, contaminated by wavy texture. These results are compared with some representative previous models.     

Kinetics of protein-release by an aptamer-based DNA nanodevice

A recently introduced DNA nanodevice can be used to selectively bind or release the protein thrombin triggered by DNA effector strands. The release process is not well described by simple first or second order reaction kinetics. Here, fluorescence resonance energy transfer and fluorescence correlation spectroscopy experiments are used to explore the kinetics of the release process in detail. To this end the influence of concentration variations and also of temperature is determined. The relevant kinetic parameters are extracted from these experiments and the kinetic behavior of the system is simulated numerically using a set of rate equations. The hydrodynamic radii of the aptamer device alone and bound to thrombin are determined as well as the dissociation constant for the aptamer device-thrombin complex. The results from the experiments and a numerical simulation support the view that the DNA effector strand first binds to the aptamer device followed by the displacement of the protein.     

Radial distribution function of rod-like polyelectrolytes

We study the effect of electrostatic interactions on the distribution function of the end-to-end distance of a single polyelectrolyte chain in the rod-like limit. The extent to which the radial distribution function of a polyelectrolyte is reproduced by that of a wormlike chain with an adjusted effective persistence length is investigated. Strong evidence is found for a universal scaling formula connecting the effective persistence length of a polyelectrolyte with the strength of the electrostatic interaction and the Debye screening length. Received 4 March 2002 and Received in final form 1 July 2002 RID="a" ID="a"e-mail: jrudnick@physics.ucla.edu     

Force-extension behavior of folding polymers

The elastic response of flexible polymers made of elements which can be either folded or unfolded, having different lengths in these two states, is discussed. These situations are common for biopolymers as a result of folding interactions intrinsic to the monomers, or as a result of binding of other smaller molecules along the polymer length. Using simple flexible-chain models, we show that even when the energy ε associated with maintaining the folded state is comparable to k _B T, the elastic response of such a chain can mimic usual polymer linear elasticity, but with a force scale enhanced above that expected from the flexibility of the chain backbone. We discuss recent experiments on single-stranded DNA, chromatin fiber and double-stranded DNA with proteins weakly absorbed along its length which show this effect. Effects of polymer semiflexiblity and torsional stiffness relevant to experiments on proteins binding to dsDNA are analyzed. We finally discuss the competition between electrostatic self-repulsion and folding interactions responsible for the complex elastic response of single-stranded DNA. Received 7 August 2002 and Received in final form 7 March 2003 / Published online: 15 April 2003 RID="a" ID="a"e-mail: jmarko@uic.edu     

Parametrization of the hybrid potential for pairs of neutral atoms

The hybrid form is a combination of the Rydberg potential and the London inverse-sixth-power energy. It is accurate at all relevant distance scales and simple enough for use in all-atom simulations of biomolecules. One may compute the parameters of the hybrid potential for the ground state of a pair of neutral atoms from their internuclear separation, the depth and curvature of their potential at its minimum, and from their van der Waals coefficient of dispersion C₆.     

Growth of attached actin filaments

In several studies of actin-based cellular motility, the barbed ends of actin filaments have been observed to be attached to moving obstacles. Filament growth in the presence of such filament-obstacle interactions is studied via Brownian dynamics simulations of a three-dimensional energy-based model. We find that with a binding energy greater than 24k _B T and a highly directional force field, a single actin filament is able to push a small obstacle for over a second at a speed of half of the free filament elongation rate. These results are consistent with experimental observations of plastic beads in cell extracts. Calculations of an external force acting on a single-filament-pushed obstacle show that for typical in vitro free-actin concentrations, a 3pN pulling force maximizes the obstacle speed, while a 4pN pushing force almost stops the obstacle. Extension of the model to treat beads propelled by many filaments suggests that most of the propulsive force could be generated by attached filaments.     

Interactions between isolated nucleosome core particles: A tail-bridging effect?

Interactions between isolated nucleosome core particles are studied as a function of the monovalent salt concentration by osmometry and by electrophoretic mobility measurements. The data are compared to the measurements performed on the protein-free DNA fragments and also analysed using the conventional theoretical approach. At low salt, an electrostatic screening effect accounts for the variation of the second virial coefficient whereas the simple hard-core contribution becomes predominant at high salt. In the intermediate range, an attraction occurs. In the light of previous results (Mangenot et al. Biophys. J. 82, 345 (2002)), we show that the flexible basic proteic tails are responsible for this attraction. A tail-bridging effect is discussed. Received 4 October 2001     

Formation and manipulation of regular metallic nanoparticle arrays on bacterial surface layers: an advanced TEM study

The template-directed formation of regular nanoparticle arrays on two-dimensional crystalline protein layers after their treatment with metal salt complexes was studied by transmission electron microscopy. For these investigations, bacterial surface layers (S layers), recrystallized in vitro into sheets and tube-shaped protein crystals with typical dimensions in the micrometer range, were used as the template. As identified by electron holography and scanning force microscopy, the S-layer tubes form alternating double layers when deposited onto a solid substrate surface. Two distinct pathways for the metal particle formation at the templates have been found: the site-specific growth of metal clusters by chemical reduction of the metal salt complexes, and the electron-beam induced growth of nanoparticles in the transmission electron microscope. Both mechanisms lead to regular arrays with particle densities > 6×10¹¹ cm ^-2. Nanoparticle formation by electron exposure takes exclusively place in the flat-lying double-layered protein tubes, where a sufficient amount of metal complexes can be accumulated during sample preparation. Received 6 December 2000     

X-ray reflectivity of solid-supported, multilamellar membranes

We have investigated the structure of solid-supported, multilamellar membranes by X-ray reflectivity. The density profile is obtained by fitting the full q-range to a model using the bilayer Fourier coefficients as fitting parameters. The effect of hydration and the substrate boundary condition are discussed in view of the well-known Landau-Peierls effect and its implications for structure determination. The resulting bilayer density profile agrees remarkably well with previously published data of a molecular dynamics (MD) simulation for 1,2-oleoyl-palmitoyl-sn-glycero-3-phosphocholine (OPPC). Received 1 October 2001 and Received in final form 21 December 2001     

Deformation in cooperative molecular motors

We implement a model to represent the effect of the deformation of the backbone of a system of motor proteins while sliding on a track filament. This model incorporates a nearest neighbor interaction term among the motors for the deformation energy. Correlations induced by this term result in increased motor force for inter-particle distances small compared to the ratchet period. Received 20 February 2001 and Received in final form 31 May 2001     

Polyelectrolyte chains in poor solvent. A variational description of necklace formation

We study the properties of polyelectrolyte chains under different solvent conditions, using a variational technique. The free energy and the conformational properties of a polyelectrolyte chain are studied by minimizing the free energy F_N, depending on N(N - 1)/2 trial probabilities that characterize the conformation of the chain. The Gaussian approximation is considered for a ring of length 2⁴ < N < 2⁸ and for an open chain of length 50 < N < 200 in poor- and theta-solvent conditions, including a Coulomb repulsion between the monomers. In theta-solvent conditions the blob size is measured and found in agreement with scaling theory, including charge depletion effects, expected for the case of an open chain. In poor-solvent conditions, a globule instability, driven by electrostatic repulsion, is observed. We notice also inhomogeneous behavior of the monomer-monomer correlation function, reminiscence of necklace formation in poor-solvent polyelectrolyte solutions. A global phase diagram in terms of solvent quality and inverse Bjerrum length is presented. Received 7 June 2001 and Received in final form 17 October 2001     

Laser cooling of molecules via single spontaneous emission

A general scheme for reducing the center-of-mass entropy is proposed. It is based on the repetition of a cycle, composed of three concepts: velocity selection, deceleration and irreversible accumulation. Well-known laser techniques are used to represent these concepts: Raman π-pulse for velocity selection, STIRAP for deceleration, and a single spontaneous emission for irreversible accumulation. No closed pumping cycle nor repeated spontaneous emissions are required, so the scheme is applicable to cool a molecular gas. The quantum dynamics are analytically modelled using the density matrix. It is shown that during the coherent processes the gas is translationally cooled. The internal states serve as an entropy sink, in addition to spontaneous emission. This scheme provides new possibilities to translationally laser-cool molecules for high precision molecular spectroscopy and interferometry. Received 25 June 2002 / Received in final form 28 September 2002 Published online 12 November 2002 RID="a" ID="a"e-mail: ooi@spock.physik.uni-konstanz.de RID="b" ID="b"e-mail: Peter.Marzlin@uni-konstanz.de RID="c" ID="c"e-mail: Juergen.Audretsch@uni-konstanz.de