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Daan Frenkel

Publications and source records attributed to Daan Frenkel.

At least 19 recordsLinked to original sources
PubMed2006

Translocation boost protein-folding efficiency of double-barreled chaperonins.

Incorrect folding of proteins in living cells may lead to malfunctioning of the cell machinery. To prevent such cellular disasters from happening, all cells contain molecular chaperones that assist nonnative proteins in folding into the correct native structure. One of the most studied chaperone complexes is the GroEL-GroES complex. The GroEL part has a "double-barrel" structure, which consists of two cylindrical chambers joined at the bottom in a symmetrical fashion. The hydrophobic rim of one of the GroEL chambers captures nonnative proteins. The GroES part acts as a lid that temporarily closes the filled chamber during the folding process. Several capture-folding-release cycles are required before the nonnative protein reaches its native state. Here we report molecular simulations that suggest that translocation of the nonnative protein through the equatorial plane of the complex boosts the efficiency of the chaperonin action. If the target protein is correctly folded after translocation, it is released. However, if it is still nonnative, it is likely to remain trapped in the second chamber, which then closes to start a reverse translocation process. This shuttling back and forth continues until the protein is correctly folded. Our model provides a natural explanation for the prevalence of double-barreled chaperonins. Moreover, we argue that internal folding is both more efficient and safer than a scenario where partially refolded proteins escape from the complex before being recaptured.

Binding Sites↗
PubMed2006

Simulating rare events in equilibrium or nonequilibrium stochastic systems.

We present three algorithms for calculating rate constants and sampling transition paths for rare events in simulations with stochastic dynamics. The methods do not require a priori knowledge of the phase-space density and are suitable for equilibrium or nonequilibrium systems in stationary state. All the methods use a series of interfaces in phase space, between the initial and final states, to generate transition paths as chains of connected partial paths, in a ratchetlike manner. No assumptions are made about the distribution of paths at the interfaces. The three methods differ in the way that the transition path ensemble is generated. We apply the algorithms to kinetic Monte Carlo simulations of a genetic switch and to Langevin dynamics simulations of intermittently driven polymer translocation through a pore. We find that the three methods are all of comparable efficiency, and that all the methods are much more efficient than brute-force simulation.

Journal Article↗
PubMed2005

Pore nucleation in mechanically stretched bilayer membranes.

We report a computer-simulation study of the free-energy barrier for the nucleation of pores in the bilayer membrane under constant stretching lateral pressure. We find that incipient pores are hydrophobic but as the lateral size of the pore nucleus becomes comparable with the molecular length, the pore becomes hydrophilic. In agreement with previous investigations, we find that the dynamical process of growth and closure of hydrophilic pores is controlled by the competition between the surface tension of the membrane and the line tension associated with the rim of the pore. We estimate the line tension of a hydrophilic pore from the shape of the computed free-energy barriers. The line tension thus computed is in a good agreement with available experimental data. We also estimate the line tension of hydrophobic pores at both macroscopic and microscopic levels. The comparison of line tensions at these two different levels indicates that the "microscopic" line tension should be carefully distinguished from the "macroscopic" effective line tension used in the theoretical analysis of pore nucleation. The overall shape of the free-energy barrier for pore nucleation shows no indication for the existence of a metastable intermediate during pore nucleation.

Computer Simulation↗
PubMed2005

Novel Monte Carlo scheme for systems with short-ranged interactions.

We propose a Monte Carlo (MC) sampling algorithm to simulate systems of particles interacting via very short-ranged discontinuous potentials. Such models are often used to describe protein solutions or colloidal suspensions. Most normal MC algorithms fail for such systems because, at low temperatures, they tend to get trapped in local potential-energy local minima due to the short range of the pair potential. To circumvent this problem, we have devised a scheme that changes the construction of trial moves in such a way that the potential-energy difference between initial and final states drops out of the acceptance rule for the Monte Carlo trial moves. This approach allows us to simulate systems with short-ranged attraction under conditions that were unreachable up to now.

Journal Article↗
PubMed2005

Modeling flexible amphiphilic bilayers: a solvent-free off-lattice Monte Carlo study.

We present a simple, implicit-solvent model for fluid bilayer membranes. The model was designed to reproduce the elastic properties of real bilayer membranes. For this model, we observed the solid-fluid transition and studied the in-plane diffusivity of the fluid phase. As a test, we compute the elastic-bending and area-compressing moduli of fluid bilayer membranes. We find that the computed elastic properties are consistent with the available experimental data.

Journal Article↗
PubMed2005

Surface and bulk dissolution properties, and selectivity of DNA-linked nanoparticle assemblies.

Using a simple mean-field model, we analyze the surface and bulk dissolution properties of DNA-linked nanoparticle assemblies. We find that the dissolution temperature and the sharpness of the dissolution profiles increase with the grafting density of the single-stranded DNA "probes" on the surface of colloids. The surface grafting density is controlled by the linker occupation number, in analogy with quantum particles obeying fractional statistics. The dissolution temperature increases logarithmically with the salt concentration. This is in agreement with the experimental findings [R. Jin, G. Wu, Z. Li, C. A. Mirkin, and G. C. Schatz, J. Am. Chem. Soc. 125, 1643 (2003)]. By exploiting the unique phase behavior of DNA-coated colloids, it should be possible to detect multiple "targets" in a single experiment by essentially mapping the DNA base-pair sequence onto the phase behavior of DNA-linked nanoparticle solution.

Algorithms↗
PubMed2005

Modeling the phase diagram of carbon.

We determined the phase diagram involving diamond, graphite, and liquid carbon using a recently developed semiempirical potential. Using accurate free-energy calculations, we computed the solid-solid and solid-liquid phase boundaries for pressures and temperatures up to 400 GPa and 12 000 K, respectively. The graphite-diamond transition line that we computed is in good agreement with experimental data, confirming the accuracy of the employed empirical potential. On the basis of the computed slope of the graphite melting line, we rule out the hotly debated liquid-liquid phase transition of carbon. Our simulations allow us to give accurate estimates of the location of the diamond melting curve and of the graphite-diamond-liquid triple point.

Journal Article↗
PubMed2005

Structural arrest in an ideal gas.

We report a molecular dynamics study of a simple model system that has the static properties of an ideal gas, yet exhibits nontrivial "glassy" dynamics behavior at high densities. The constituent molecules of this system are constructs of three infinitely thin hard rods of length L, rigidly joined at their midpoints. The crosses have random but fixed orientation. The static properties of this system are those of an ideal gas, and its collision frequency can be computed analytically. For number densities NL(3)/V>>1, the single-particle diffusivity goes to zero. As the system is completely structureless, standard mode-coupling theory cannot describe the observed structural arrest. Nevertheless, the system exhibits many dynamical features that appear to be mode-coupling-like. All high-density incoherent intermediate scattering functions collapse onto master curves that depend only on the wave vector.

Journal Article↗
PubMed2005

Monte Carlo study of hard pentagons.

How does a liquid freeze if the geometry of its particles conflicts with the symmetry of the crystal it should naturally form? We study this question in the simplest model system of particles exhibiting such a symmetry mismatch: hard pentagons in two dimensions. Using isobaric and isotensic Monte Carlo simulations we have studied the phase behavior of hard pentagons. On increasing the pressure from the homogeneous and isotropic low-density phase, the system first exhibits a rotator phase (plastic solid) with a triangular lattice structure. At higher densities it undergoes a weak first-order phase transition into a "striped" phase composed of alternating rows of oppositely pointing particles. This phase is analogous to the "striped" phase in the compressible antiferromagnetic Ising model on a triangular lattice and is an example of systems in which frustration due to the mismatch in symmetries is released by an elastic coupling to the lattice. In order to pursue this analogy we also consider hard heptagons, showing that in this case the decrease in symmetry mismatch indeed leads to a shift in the transition densities to higher values and a weakening of the transition.

Journal Article↗
PubMed2005

Force barriers for membrane tube formation.

We used optical tweezers to measure the force-extension curve for the formation of tubes from giant vesicles. We show that a significant force barrier exists for the formation of tubes, which increases linearly with the radius of the area on which the pulling force is exerted. The tubes form through a first-order transition with accompanying hysteresis. We confirm these results with Monte Carlo simulations and theoretical calculations. Whether membrane tubes can be formed in, for example, biological cells, thus depends on the details of how forces are applied.

Biotin↗
PubMed2005

Oriented primary crystal nucleation in lamellar diblock copolymer systems.

We report a numerical study of the primary crystal nucleation of diblock copolymers in a lamellar phase. Only one of two polymer blocks is crystallizable; the other is maintained in a glassy state. We find that crystals in this lamellar geometry tend to nucleate with the chain axis perpendicular to the lamellar plane. However, if in the same lamellar structure, we break the junction between the crystallizable and non-crystallizable blocks of the polymers, we find that crystallites tend to align parallel to the lamellar plane. This observation clarifies the molecular origin of the competition between parallel and perpendicular crystallite orientations in real block-copolymer systems.

Journal Article↗
PubMed2004

Speed-up of Monte Carlo simulations by sampling of rejected states.

The Markov chain Monte Carlo method is an important tool to estimate the average properties of systems with a very large number of accessible states. This technique is used extensively in fields ranging from physics to genetics and economics. The rejection of trial configurations is a central ingredient in existing Markov chain Monte Carlo simulations. I argue that the efficiency of Monte Carlo simulations can be enhanced, sometimes dramatically, by properly sampling configurations that are normally rejected. This "waste-recycling" of microstates is useful in sampling schemes in which only one of a large set of trial configurations is accepted. It differs fundamentally from schemes that extract information about the density of macrostates from virtual Monte Carlo moves. As a simple illustration, I show that the method greatly improves the calculation of the order-parameter distribution of a two-dimensional Ising model. This method should enhance the efficiency of parallel Monte Carlo simulations significantly.

Journal Article↗
PubMed2004

Designing specificity of protein-substrate interactions.

One of the key properties of biological molecules is that they can bind strongly to certain substrates yet interact only weakly with the very large number of other molecules that they encounter. Using a simple lattice model, we test several methods to design molecule-substrate binding specificity. We characterize the binding free energy and binding energy as a function of the size of the interacting units. Our simulations indicate that there exists a temperature window where specific binding is possible. Binding sites that have been designed to interact quite strongly with specific substrates are unlikely to bind nonspecifically to other substrates. In other words, the conflict between specific interactions between small numbers of biomolecules and weak, nonspecific interaction with the rest need not be a very serious design constraint.

Amino Acid Sequence↗
PubMed2004

The steady state of heterogeneous catalysis, studied by first-principles statistical mechanics.

The turnover frequency of the catalytic oxidation of CO at RuO2(110) was calculated as a function of temperature and partial pressures using ab initio statistical mechanics. The underlying energetics of the gas-phase molecules, dissociation, adsorption, surface diffusion, surface chemical reactions, and desorption were obtained by all-electron density-functional theory. The resulting CO2 formation rate [in the full (T,p(CO),p(O2)) space], the movies displaying the atomic motion and reactions over times scales from picoseconds to seconds, and the statistical analyses provide insight into the concerted actions ruling heterogeneous catalysis and open thermodynamic systems in general.

Journal Article↗
PubMed2004

Crystal nucleation of colloidal suspensions under shear.

We use Brownian dynamics simulations in combination with the umbrella sampling technique to study the effect of shear flow on homogeneous crystal nucleation. We find that a homogeneous shear rate leads to a significant suppression of the crystal nucleation rate and to an increase of the size of the critical nucleus. A simple, phenomenological extension of classical nucleation theory accounts for these observations. The orientation of the crystal nucleus is tilted with respect to the shear direction.

Biophysical Phenomena↗
PubMed2004

Discrete solution of the electrokinetic equations.

We present a robust scheme for solving the electrokinetic equations. This goal is achieved by combining the lattice-Boltzmann method with a discrete solution of the convection-diffusion equation for the different charged and neutral species that compose the fluid. The method is based on identifying the elementary fluxes between nodes, which ensures the absence of spurious fluxes in equilibrium. We show how the model is suitable to study electro-osmotic flows. As an illustration, we show that, by introducing appropriate dynamic rules in the presence of solid interfaces, we can compute the sedimentation velocity (and hence the sedimentation potential) of a charged sphere. Our approach does not assume linearization of the Poisson-Boltzmann equation and allows us for a wide variation of the Peclet number.

Journal Article↗