Molecular Dynamics Studies of Diffusion in Model Cylindrical Pores at Very Low Densities

Abstract

Molecular dynamics simulation has been used to study diffusion of methane at ambient temperature in cylindrical pores at very low densities. The cylinders were modelled as a continuum solid which interacts with the methane in the radial direction only. At the lowest densities, the VACF method does not yield reliable values of the self diffusion coefficient, D_s , but a suitable choice of time step and run length enables values of D_s to be found from MSD plots that are below the classical Knudsen diffusion coefficients. When density is increased, D_s passes through a maximum although the adsorption isotherm remains inside the Henry law region. Maxima are found for two cylinder radii and for two adsorbent field strengths. The existence of a maximum is attributed to transient intermolecular interactions. Analysis of a molecular trajectory demonstrates that long diffusion paths can be triggered by the rare event of an intermolecular encounter which forces a molecule into the repulsive part of the wall potential. At sufficiently high density, subsequent collisions quench the tendency towards long paths, and D_s decreases again. The issue of simulation artefact as a source of these observations is discussed.     

Simulation of Lamellar Phase Transitions in Block Copolymers and Surfactants

Abstract

Simulations of the lamellar phase transitions of symmetric amphiphilic chains are carried out on a cubic lattice, with the amphiphilic chain length N varied from 6 to 48 lattice sites, corresponding to lengths ranging from surfactants to short block copolymers. We find that the effective interaction energy parameter χN (which incorporates the effect of added solvant) at which the transition from the lamellar ordered state to the disordered state occurs is roughly equal to 18-21. While this result is consistent with an extrapolation of the Fredrickson-Helfand weak-segragation theory to N values in the range of the simulations, the amplitude of the sinusoidal compositional wave in the ordered state near the transition is large for all N studied, in disagreement with the weak segregation theories. Thus, for values of N up to 48, the transition occurs in a “moderate,” rather than weak-segregation regime. Near the disordering transition, fluctuating “bridge” or “hole” defects in the lamellae spontaneously appear; with heating these proliferate and lead to the disordering transition. These fluctuating bridges might help explain anomalous diffusion and rheological behavior observed near the disordering transition. We also find that in the ordered state near the transition, the orientational order parameter, which is proportional to the intrinsic birefringence, falls rapidly with increasing N, roughly as 1.5 N^-2.     

The Behaviour of Ions in Narrow Water-Filled Pores

Today, the equilibrium behavior of ions in solution may be predicted with some confidence, essentially because rapid ionic diffusion over small distances ensures homogeneity throughout the solution. Equilibrium concepts such as ionic strength and pH apply. However, when attempting to understand the behavior of ions passing rapidly through narrow pores such as ion channels, no such equilibrium state may be assumed. The passing solution may have been in equilibrium with conditions at the mouth of the pore but will not be in equilibrium with charged molecules on the pore wall. In addition, the water in narrow pores will be partially ordered by contact with the pore walls and will not behave like bulk water.To illustrate this difference, a simple equilibrium calculation of the ion concentrations near a plastic sheet penetrated by narrow pores and containing in its surface partially ionized carboxyl groups is shown to be in good agreement with experiment. However, to predict the non-equilibrium behavior within the narrow pores is much more difficult. To illustrate the difficulty, a Monte Carlo computer model is described which attempts to predict the rapid switching of ion current observed experimentally with these narrow pores.     

Vapour-Liquid Phase Equilibria of n-alkanes by Direct Monte Carlo Simulations

Abstract

We report results of direct Monte Carlo simulations of n-pentane and n-decane at the liquidvapour interface for a number of temperatures. The intermolecular interactions are modeled using the last version of the anisotropic united atom model (AUA4). We have used the local long range correction energy and an algorithm allowing to select randomly with equal probability two different displacements. The liquid and vapour densities are in excellent agreement with experimental data and with those previously calculated using the GEMC method.     

Molecular Dynamics Simulations of some Small Organic Molecules

Abstract

Free energy differences between different conformers of D-ribofuranose, L-malic acid and meso-tartaric acid in solution were calculated using Molecular Dynamics simulations. In case of ribose the α → β transition was studied. For the acids attention was focussed on the transitions between the three possible staggered conformers with respect to the central C-C bond. In all cases a thermodynamic integration method was employed to evaluate the free energy difference. The use of an alternative technique, umbrella sampling, for ribose did not give promising results.

It was shown that one needs a fairly accurate picture of the accessible conformational space in case of flexible molecules like the ones considered here before one can determine meaningful free energy differences. Large hysteresis effects between forward and reverse simulated transitions were observed, but contrary to the general belief they are no direct measure of the accuracy of the calculated ΔG values. In all cases the ΔG values resulting from the simulations and from NMR experiments agree within the, considerable, error limits and for the different forms of D-ribose, L-malic acid and L-tartaric acid the relative order of their populations is also correctly reproduced.     

Spatiotemporal Control of Intracellular Phase Transitions Using Light-Activated optoDroplets

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Condensed State Molecular Dynamics in Sorbitol and Maltitol: Mobility Gradients and Conformation Transitions

Abstract

Molecular mobility in sorbitol and maltitol is studied in order to understand their differences near the junction between the α and β relaxations. The molecular dynamics simulations performed on the polyols in their bulk state give support to the ¹³C NMR results and imply that the mobility of a carbon atom located at the extremity of the chain is higher than that of any other carbon. Moreover, the difference in carbon atoms mobility is greater within the sorbitol moiety of maltitol than in sorbitol and seems intimately related to the junction temperature of the α and β relaxation processes. The reorientation of the C–H vectors as probed by NMR is shown to be mainly the effect of conformation transitions in the case of a carbon atom located at the end of the chain.     

Phase transitions and permeability changes in dry membranes during rehydration

Dry phospholipid bilayers are known to undergo transient changes in permeability during rehydration. In this review, we present evidence from which we suggest that this permeability change is due to a gel to liquid-crystaline phase transition accompanying rehydration. If the transition is avoided, as in lipids that remain in gel phase whether dry or rehydrated, the problem of leakage during rehydration is obviated, at least in part. Further, the evidence that the transition temperature for dry bilayers can be depressed by certain sugars is discussed. Finally, we show that these principles can be extended to intact cells. Using pollen grains as a model, we have measured the transition temperature for membrane phospholipids and show that the transition is correlated with physiological measurements including permeability changes and subsequent germination. From theT_m values taken from pollen grains at different water contents, we have constructed a phase diagram for the intact pollen that has high predictive value for physiological properties.     

Molecular Simulations of a Dynamic Protein Complex: Role of Salt-Bridges and Polar Interactions in Configurational Transitions

Ion charge pairs and hydrogen bonds have been extensively studied for their roles in stabilizing protein complexes and in steering the process of protein association. Recently, it has become clear that some protein complexes are dynamic in that they interconvert between several alternate configurations. We have previously characterized one such system: the EphA2:SHIP2 SAM-SAM heterodimer by solution NMR. Here we carried out extensive all-atom molecular-dynamics simulations on a microsecond time-scale starting with different NMR-derived structures for the complex. Transitions are observed between several discernible configurations at average time intervals of 50–100 ns. The domains reorient relative to one another by substantial rotation and a slight shifting of the interfaces. Bifurcated and intermediary salt-bridge and hydrogen-bond interactions play a role in the transitions in a process that can be described as moving along a “monkey-bar”. We notice an increased density of salt bridges near protein interaction surfaces that appear to enable these transitions, also suggesting why the trajectories can become kinetically hindered in regions where fewer of such interactions are possible. In this context, even microsecond molecular-dynamics simulations are not sufficient to sample the energy landscape unless the structures remain close to their experimentally derived low-energy configurations.     

Molecular Simulations of a Dynamic Protein Complex: Role of Salt-Bridges and Polar Interactions in Configurational Transitions

Ion charge pairs and hydrogen bonds have been extensively studied for their roles in stabilizing protein complexes and in steering the process of protein association. Recently, it has become clear that some protein complexes are dynamic in that they interconvert between several alternate configurations. We have previously characterized one such system: the EphA2:SHIP2 SAM-SAM heterodimer by solution NMR. Here we carried out extensive all-atom molecular-dynamics simulations on a microsecond time-scale starting with different NMR-derived structures for the complex. Transitions are observed between several discernible configurations at average time intervals of 50–100 ns. The domains reorient relative to one another by substantial rotation and a slight shifting of the interfaces. Bifurcated and intermediary salt-bridge and hydrogen-bond interactions play a role in the transitions in a process that can be described as moving along a “monkey-bar”. We notice an increased density of salt bridges near protein interaction surfaces that appear to enable these transitions, also suggesting why the trajectories can become kinetically hindered in regions where fewer of such interactions are possible. In this context, even microsecond molecular-dynamics simulations are not sufficient to sample the energy landscape unless the structures remain close to their experimentally derived low-energy configurations.     

Formation of Transient Non-Protein Calcium Pores by Lysophospholipids in S49Lymphoma cells

Palmitoyl-lysophosphatidylcholine promotes a transient calcium influx in lymphoma cells. Previously, it was observed that this influx was accompanied by a temporary increase in propidium iodide permeability that appeared linked to calcium entry. Those studies demonstrated that cobalt or nickel could block the response to lysophosphatidylcholine and raised the question of whether the calcium conductance involved specific channels. This communication describes a series of experiments to address that issue. The time dependence and structural specificity of the responses to lysophosphatidylcholine reinforced the hypothesis of a specific channel or transporter. Nevertheless, observations using patch clamp or calcium channel blockers suggested that this “channel” does not involve proteins. Alternative protein-mediated mechanisms such as indirect involvement of the sodium-calcium exchanger and the sodium-potassium ATPase were also excluded. Experiments with extracellular and intracellular calcium chelators suggested a common route of entry for calcium and propidium iodide. More directly, the ability of lysophosphatidylcholine to produce cobalt-sensitive permeability to propidium iodide was reproduced in protein-free artificial membranes. Finally, the transient nature of the calcium time course was rationalized quantitatively by the kinetics of lysophosphatidylcholine metabolism. These results suggest that physiological concentrations of lysophosphatidylcholine can directly produce membrane pores that mimic some of the properties of specific protein channels.This revised version was published online in June 2005 with a corrected cover date.     

Dynamics of Allosteric Transitions in Dynein

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Molecular Dynamics Simulations of the Unfolding of the Starch Binding Domain from Aspergillus niger Glucoamylase

Abstract

The 600 ps molecular dynamics simulations to investigate the unfolding of the starch binding domain from Aspergillus niger glucoamylase were conducted in vacuum as well as in an external field with the dielectric constant of 80 with temperature jump technique. Electrostatic interactions play an important role in determining the stability of the β-strands in this domain. The starch binding site 1 is less stable than site 2 since it is more exposed to the surface. The disulfide bond between C509 and C604 is unstable since these two residues are located near the flexible linker domain and in the mobile loop region between β-strands 6 and 7, respectively. The melting temperature, at which the total residual β-strand content is 50% that of the solution structure, is about 544K for the simulations with dielectric constant of 80, leading to the estimated unfolding timescale of 0.48 ms in vitro. In addition, the unfolding of the starch binding domain is proposed to initiate from the interior region by the lost of the integrity of the secondary structure.     

Molecular Dynamics Simulations of the Unfolding Mechanism of the Catalytic Domain from Aspergillus awamori var. X100 Glucoamylase

Abstract

In this study, 200 ps molecular dynamics simulations were conducted to investigate the unfolding mechanism of the catalytic domain of glucoamylase from Aspergillus awamori var. X100. The unfolding of this domain was suggested to follow a putative hierarchical manner, in which the heavily O-glycosylated belt region from residues T440 to A471 acted as the initiation site, followed by the a-helix secondary structure destruction, and then the collapse of the catalytic center pocket. The O-glycosylated belt region surrounded the surface of the catalytic domain in its native state at low temperature, whereas it was extended and is more suitable to be classified as part of the subsequent linker domain at high temperatures due to its high flexibility. The inner set helices of the (α/α)₆-barrel seemed to exhibit higher helical content than the outer set ones at all temperatures examined. The distances between the C_α of the three Cys residue pairs fluctuated rapidly at higher temperatures, indicating that these disulfide bonds have little effect on the structural stabilization. The melting temperature, at which the residual total helicity of the catalytic domain is 50%, is much lower than the critical temperature, at which the catalytic center pocket has lost its structural integrity.     

NMR evidence of hydrogen bonding in 1-ethyl-3-methylimidazolium-tetrafluoroborate room temperature ionic liquid

The 1-ethyl-3-methylimidazolium-tetrafluoroborate (EMI–BF₄) room temperature ionic liquid was investigated with NMR techniques. Diffusion coefficients measured at temperatures ranging from 300 to 360 K indicate that phase-change occurred in the vicinity of 333 K, which is supported by ¹¹B quadrupolar relaxation rates. This phase change is ascribed to the transformation of the diffusion particle from ‘discrete ion-pair’ to ‘individual ion’ at temperatures above 335 K due to decomposition of the EMI–BF₄ ion pair. Analysis of the ¹³C dipole–dipole relaxation rates identifies the formation of hydrogen bond (C2HF) between the counterions, EMI⁺ and BF₄ ⁻. This hydrogen bonding may have significant contribution to the higher viscosity of this ionic liquid in comparison with the EMI–AlCl₄ ionic liquid at corresponding temperatures.     

Spermiogenesis in three species of cicadas (Hemiptera: Cicadidae)

Spermiogenesis in three species of cicadas representing one cicadettine (Monomatapa matoposa Boulard) and two cicadines (Diceroprocta biconica [Walker] and Kongota punctigera [Walker]) was investigated by light and electron microscopy. Although spermiogenesis was occurring in the testis of adult males of all species, earlier spermiogenic stages were observed in D. biconica only. While spermiogenesis was similar to that described for other insects, some differences were noted. For example granular material did not assemble around the centriole to form a centriolar adjunct but did accumulate in the cytoplasm of early spermatids adjacent to a region of the nuclear membrane where nuclear pores were aggregated. In late spermatids this material accumulated anterior to the mitochondrial derivatives in a developing postero‐lateral nuclear groove. While this material has been named the ‘centriolar adjunct’ by previous authors, its formation away from the centriole raises questions about its true identity. Second, during acrosome maturation an ante‐acrosomal region of cytoplasm develops. Although present in later spermatids, this region is lost in spermatozoa. Interspecific variations in chromatin condensation patterns and the number of microtubule layers encircling the spermatid nucleus during spermiogenesis were noted.     

Molecular Dynamics Simulation Studies of the Density and Temperature Dependence of Self-diffusion in a Cylindrical Micropore

We report Molecular Dynamics calculations of radial density profiles and self-diffusion coefficients of Lennard-Jones fluids in a cylindrical pore of radius 2σ, for a wide range of temperatures and densities. At n _p σ³ = 0.825 the self-diffusion coefficient parallel to the pore walls D _∥*. follows a monotonic (nearly linear) increase with kT/ε and is very similar to that of the bulk self-diffusion coefficient D _b *. At n _p σ³ = 0.4 and kT/ε ≤ 1.0 the curve of D _∥* vs. kT/ε shows a distinct inflection in the region 0.7 ≤ kT/ε ≤ 0.9 and values of D _∥* are much less than D _b * decreasing to near solid state values at very low temperatures. At the highest temperature studied, kT/ε = 2.98, D _∥* is almost inversely proportional to density and in a fairly close agreement with that of D _b *. At KT/ε = 0.49, D _∥* is much smaller than D _b *. The motion of adsorbate particles normal to the walls is also discussed.     

High-pressure Sapphire Cell for Phase Equilibria Measurements of CO2/Organic/Water Systems

The high pressure sapphire cell apparatus was constructed to visually determine the composition of multiphase systems without physical sampling. Specifically, the sapphire cell enables visual data collection from multiple loadings to solve a set of material balances to precisely determine phase composition. Ternary phase diagrams can then be established to determine the proportion of each component in each phase at a given condition. In principle, any ternary system can be studied although ternary systems (gas-liquid-liquid) are the specific examples discussed herein. For instance, the ternary THF-Water-CO₂ system was studied at 25 and 40 °C and is described herein. Of key importance, this technique does not require sampling. Circumventing the possible disturbance of the system equilibrium upon sampling, inherent measurement errors, and technical difficulties of physically sampling under pressure is a significant benefit of this technique. Perhaps as important, the sapphire cell also enables the direct visual observation of the phase behavior. In fact, as the CO₂ pressure is increased, the homogeneous THF-Water solution phase splits at about 2 MPa. With this technique, it was possible to easily and clearly observe the cloud point and determine the composition of the newly formed phases as a function of pressure.The data acquired with the sapphire cell technique can be used for many applications. In our case, we measured swelling and composition for tunable solvents, like gas-expanded liquids, gas-expanded ionic liquids and Organic Aqueous Tunable Systems (OATS)^1-4. For the latest system, OATS, the high-pressure sapphire cell enabled the study of (1) phase behavior as a function of pressure and temperature, (2) composition of each phase (gas-liquid-liquid) as a function of pressure and temperature and (3) catalyst partitioning in the two liquid phases as a function of pressure and composition. Finally, the sapphire cell is an especially effective tool to gather accurate and reproducible measurements in a timely fashion.     

Molecular Dynamics Study of Nitrogen in Slit Micropores

Abstract

We present results of a computer simulation study of fluid nitrogen in model slit micropores. The model used for the micropore allows for the permeability of the pore wall to the confined fluid to be precisely controlled, while maintaining the atomic nature of the wall. Density and orientation profiles, wall permeabilities and diffusion coefficients have been obtained for systems with pore walls ranging from the almost impermeable to the completely permeable. Both the density and orientation profiles exhibit nonuniform behavior, while we observe anisotropy in the diffusion coefficients.