Search PubMed⌕ Search

Biomedical subjects

Daan Frenkel

Publications and source records attributed to Daan Frenkel.

At least 19 recordsLinked to original sources
PubMed2006

Monte Carlo study of substrate-induced folding and refolding of lattice proteins.

Many proteins can switch from one conformation to another under the influence of an external driving force, such as the binding to a specific substrate. Using a simple lattice model we show that it is feasible to design protein-like lattice proteins that can have two different conformations, depending on whether or not they are bound to a substrate. We give three different examples of such substrate-induced refolding. In addition, we have explored substrate-induced folding of lattice proteins that do not fold when free in solution. We show that such proteins can bind with the same high specificity as prefolded protein, but have a considerably lower binding free energy. In this way proteins can bind to a substrate in a way that is highly specific, yet reversible.

Amino Acid Sequence↗
PubMed2006

Application of the optimized Baxter model to the hard-core attractive Yukawa system.

We perform Monte Carlo simulations on the hard-core attractive Yukawa system to test the optimized Baxter model that was introduced by Prinsen and Odijk [J. Chem. Phys. 121, 6525 (2004)] to study a fluid phase of spherical particles interacting through a short-range pair potential. We compare the chemical potentials and pressures from the simulations with analytical predictions from the optimized Baxter model. We show that the model is accurate to within 10% over a range of volume fractions from 0.1 to 0.4, interaction strengths up to three times the thermal energy, and interaction ranges from 6% to 20% of the particle diameter, and performs even better in most cases. We furthermore establish the consistency of the model by showing that the thermodynamic properties of the Yukawa fluid computed via simulations may be understood on the basis of one similarity variable, the stickiness parameter defined within the optimized Baxter model. Finally, we show that the optimized Baxter model works significantly better than an often used, naive method determining the stickiness parameter by equating the respective second virial coefficients based on the attractive Yukawa and Baxter potentials.

Journal Article↗
PubMed2006

Forward flux sampling-type schemes for simulating rare events: efficiency analysis.

We analyze the efficiency of several simulation methods which we have recently proposed for calculating rate constants for rare events in stochastic dynamical systems in or out of equilibrium. We derive analytical expressions for the computational cost of using these methods and for the statistical error in the final estimate of the rate constant for a given computational cost. These expressions can be used to determine which method to use for a given problem, to optimize the choice of parameters, and to evaluate the significance of the results obtained. We apply the expressions to the two-dimensional nonequilibrium rare event problem proposed by Maier and Stein [Phys. Rev. E 48, 931 (1993)]. For this problem, our analysis gives accurate quantitative predictions for the computational efficiency of the three methods.

Journal Article↗
PubMed2006

Lattice-Boltzmann simulation of the sedimentation of charged disks.

We report a series of lattice-Boltzmann simulations of the sedimentation velocity of charged disks. In these simulations, we explicitly account for the hydrodynamic and electrostatic forces on disks and on their electrical double layer. By comparing our results with those for spheres with equal surface and charge, we can clarify the effect of the particle shape on the sedimentation process. We find that disks and spheres exhibit a different dependence of the sedimentation velocity on the Debye screening length. An analysis of the behavior of highly charged disks (beyond the scope of the linearized Poisson-Boltzmann equation) shows that, in that regime, the charge dependence of the sedimentation velocity of disks and spheres is similar. This suggests that, at high charge, the effective hydrodynamic shape of the disks becomes more spherical.

Anisotropy↗
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↗