Molecular dynamics simulation of organic-inorganic nanocomposites: Layering behavior and interlayer structure of organoclays

Isothermal-isobaric (NPT) molecular dynamics simulation has been performed to investigate the layering behavior and structure of nanoconfined quaternary alkylammoniums in organoclays. This work is focused on systems consisting of two clay layers and a number of alkylammoniums, and involves the use of modified Dreiding force field. The simulated basal spacings of organoclays agree satisfactorily with the experimental results in the literature. The atomic density profiles in the direction normal to the clay surface indicate that the alkyl chains within the interlayer space of montmorillonite exhibit an obvious layering behavior. The headgroups of long alkyl chains are distributed within two layers close to the clay surface, whereas the distributions of methyl and methylene groups are strongly dependent on the alkyl chain length and clay layer charge. Monolayer, bilayer, and pseudo-trilayer structures are found in organoclays modified with single long alkyl chains, which are identical to the structural models based on the measured basal spacings. A pseudo-quadrilayer structure, for the first time to our knowledge, is also identified in organoclays with double long alkyl chains. In the mixture structure of paraffin-type and multilayer, alkyl chains do not lie flat within a single layer but interlace, and also jump to the next layer in pseudo-trilayer as well as next nearest layer in pseudo-quadrilayer.

Structural plasticity in MS channels

Gating of the mechanosensitive channel MscS involves cooperative action of glycine and alanine residues along the pore-lining transmembrane helix. Opening of the channel is facilitated by an iris-like rotation and tilt of the pore-lining helices. Site-directed mutagenesis indicates that substantial structural plasticity can be tolerated by MscS without impairing its function.

Mimicking the action of GroEL in molecular dynamics simulations: Application to the refinement of protein structures

Bacterial chaperonin, GroEL, together with its co-chaperonin, GroES, facilitates the folding of a variety of polypeptides. Experiments suggest that GroEL stimulates protein folding by multiple cycles of binding and release. Misfolded proteins first bind to an exposed hydrophobic surface on GroEL. GroES then encapsulates the substrate and triggers its release into the central cavity of the GroEL/ES complex for folding. In this work, we investigate the possibility to facilitate protein folding in molecular dynamics simulations by mimicking the effects of GroEL/ES namely, repeated binding and release, together with spatial confinement. During the binding stage, the (metastable) partially folded proteins are allowed to attach spontaneously to a hydrophobic surface within the simulation box. This destabilizes the structures, which are then transferred into a spatially confined cavity for folding. The approach has been tested by attempting to refine protein structural models generated using the ROSETTA procedure for ab initio structure prediction. Dramatic improvements in regard to the deviation of protein models from the corresponding experimental structures were observed. The results suggest that the primary effects of the GroEL/ES system can be mimicked in a simple coarse-grained manner and be used to facilitate protein folding in molecular dynamics simulations. Furthermore, the results Sur port the assumption that the spatial confinement in GroEL/ES assists the folding of encapsulated proteins.

Molecular dynamics characterization of n-octyl-beta-D-glucopyranoside micelle structure in aqueous solution

n-Octyl-beta-D-glueopyranoside (OG) is a non-ionic glycolipid, which is used widely in biotechnical and biochemical applications. All-atom molecular dynamics simulations from two different initial coordinates and velocities in explicit solvent have been performed to characterize the structural behaviour of an OG aggregate at equilibrium conditions. Geometric packing properties determined from the simulations and small angle neutron scattering experiment state that OG micelles are more likely to exist in a non-spherical shape, even at the concentration range near to the critical micelle concentration (0.025 M). Despite few large deviations in the principal moment of inertia ratios, the average micelle shape calculated from both simulations is a prolate ellipsoid. The deviations at these time scales are presumably the temporary shape change of a micelle. However, the size of the micelle and the accessible surface areas were constant during the simulations with the micelle surface being rough and partially elongated. Radial distribution functions computed for the hydroxyl oxygen atoms of an OG show sharper peaks at a minimum van der Waals contact distance than the acetal oxygen, ring oxygen, and anomeric carbon atoms. This result indicates that these atoms are pointed outwards at the hydrophilic/hydrophobic interface, form hydrogen bonds with the water molecules, and thus hydrate the micelle surface effectively. (c) 2005 Elsevier Inc. All rights reserved.

Molecular dynamics simulations of the hydrophobin SC3 at a hydrophobic/hydrophilic interface

Hydrophobins are small (similar to 100 aa) proteins that have an important role in the growth and development of mycelial fungi. They are surface active and, after secretion by the fungi, self-assemble into amphipathic membranes at hydrophobic/hydrophilic interfaces, reversing the hydrophobicity of the surface. In this study, molecular dynamics simulation techniques have been used to model the process by which a specific class I hydrophobin, SC3, binds to a range of hydrophobic/ hydrophilic interfaces. The structure of SC3 used in this investigation was modeled based on the crystal structure of the class II hydrophobin HFBII using the assumption that the disulfide pairings of the eight conserved cysteine residues are maintained. The proposed model for SC3 in aqueous solution is compact and globular containing primarily P-strand and coil structures. The behavior of this model of SC3 was investigated at an air/water, an oil/water, and a hydrophobic solid/water interface. It was found that SC3 preferentially binds to the interfaces via the loop region between the third and fourth cysteine residues and that binding is associated with an increase in a-helix formation in qualitative agreement with experiment. Based on a combination of the available experiment data and the current simulation studies, we propose a possible model for SC3 self-assembly on a hydrophobic solid/water interface.

Molecular dynamics study of MscL interactions with a curved lipid bilayer

Mechanosensitivity is a ubiquitous sensory mechanism found in living organisms. The simplest known mechanotransducing mechanism is found in bacteria in the form of the mechanosensitive membrane channel of large conductance, MscL. This channel has been studied extensively using a variety of methods at a functional and structural level. The channel is gated by membrane tension in the lipid bilayer alone. It serves as a safety valve protecting bacterial cells against hypoosmotic shock. MscL of Escherichia coli embedded in bilayers composed of asymmetric amounts of single-tailed and double-tailed lipids has been shown to gate spontaneously, even in the absence of membrane tension. To gain insight into the effect of the lipid membrane composition and geometry on MscL structure, a fully solvated, all-atom model of MscL in a stress-free curved bilayer composed of double- and single-tailed lipids was studied using a 9.5-ns molecular dynamics simulation. The bilayer was modeled as a domed structure accommodating the asymmetric composition of the monolayers. During the course of the simulation a spontaneous restructuring of the periplasmic loops occurred, leading to interactions between one of the loops and phospholipid headgroups. Previous experimental studies of the role of the loops agree with the observation that opening starts with a restructuring of the periplasmic loop, suggesting an effect of the curved bilayer. Because of limited resources, only one simulation of the large system was performed. However, the results obtained suggest that through the geometry and composition of the bilayer the protein structure can be affected even on short timescales.

Structure and dynamics of a gene network model incorporating small RNAs

As advances in molecular biology continue to reveal additional layers of complexity in gene regulation, computational models need to incorporate additional features to explore the implications of new theories and hypotheses. It has recently been suggested that eukaryotic organisms owe their phenotypic complexity and diversity to the exploitation of small RNAs as signalling molecules. Previous models of genetic systems are, for several reasons, inadequate to investigate this theory. In this study, we present an artificial genome model of genetic regulatory networks based upon previous work by Torsten Reil, and demonstrate how this model generates networks with biologically plausible structural and dynamic properties. We also extend the model to explore the implications of incorporating regulation by small RNA molecules in a gene network. We demonstrate how, using these signals, highly connected networks can display dynamics that are more stable than expected given their level of connectivity.

Vibrational dynamics and structure of natural feldspars

The present study gives a contribution to the knowledge on the Na-feldspar and plagioclases, extending the database of the Raman spectra of plagioclases with different chemical compositions and structural orders. This information may be used for the future planetary explorations by “rovers”, for the investigation of ceramics nanocrystal materials and for the mineralogical phase identification in sediments. Na-feldspar and plagioclase solid solution have been investigated by Raman spectroscopy in order to determine the relationships between the vibrational changes and the plagioclase crystal chemistry and structure. We focused on the Raman micro-spectroscopy technique, being a non-destructive method, suited for contactless analysis with high spatial resolution. Chemical and structural analyses have been performed on natural samples to test the usefulness of Raman spectroscopy as a tool in the study of the pressure-induced structural deformations, the disordering processes due to change in the Al-Si distribution in the tetrahedral sites and, finally, in the determination of the anorthitic content (Anx) in plagioclase minerals. All the predicted 39 Ag Raman active modes have been identified and assigned to specific patterns of atomic vibrational motion. A detailed comparison between experimental and computed Raman spectra has been performed and previous assignments have been revised, solving some discrepancies reported in recent literature. The ab initio calculation at the hybrid HF/DFT level with the WC1LYP Hamiltonian has proven to give excellent agreement between calculated and experimentally measured Raman wavenumbers and intensities in triclinic minerals. A short digression on the 36 infrared active modes of Na-feldspar has been done too. The identification of all 39 computed Raman modes in the experimentally measured spectra of the fully ordered Na-feldspar, known as low albite, along with the detailed description of each vibrational mode, has been essential to extend the comparative analysis to the high pressure and high temperature structural forms of albite, which reflect the physical–chemical conditions of the hosting rocks. The understanding of feldspar structure response to pressure and temperature is crucial in order to constrain crustal behaviour. The compressional behaviour of the Na-feldspar has been investigated for the first time by Raman spectroscopy. The absence of phase transitions and the occurrence of two secondary compression mechanisms acting at different pressures have been confirmed. Moreover, Raman data suggest that the internal structural changes are confined to a small pressure interval, localized around 6 GPa, not spread out from 4 to 8 GPa as suggested by previous X-rays studies on elasticity. The dominant compression mechanisms act via tetrahedral tilting, while the T-O bond lengths remain nearly constant at moderate compressional regimes. At the spectroscopic level, this leads to the strong pressure dependencies of T-O-T bending modes, as found for the four modes at 478, 508, 578 and 815 cm-1. The Al-Si distribution in the tetrahedral sites affects also the Raman spectrum of Na-feldspar. In particular, peak broadening is more sensitive than peak position to changes in the degree of order. Raman spectroscopy is found to be a good probe for local ordering, in particular being sensitive to the first annealing steps, when the macroscopic order parameter is still high. Even though Raman data are scattered and there are outliers in the estimated values of the degree of order, the average peak linewidths of the Na-feldspar characteristic doublet band, labelled here as υa and υb, as a function of the order parameter Qod show interesting trends: both peak linewidths linearly increase until saturation. From Qod values lower than 0.6, peak broadening is no more affected by the Al-Si distribution. Moreover, the disordering process is found to be heterogeneous. SC-XRD and Raman data have suggested an inter-crystalline inhomogeneity of the samples, i.e., the presence of regions with different defect density on the micrometric scale. Finally, the influence of Ca-Na substitution in the plagioclase Raman spectra has been investigated. Raman spectra have been collected on a series of well characterized natural, low structural plagioclases. The variations of the Raman modes as a function of the chemical composition and the structural order have been determined. The number of the observed Raman bands at each composition gives information about the unit-cell symmetry: moving away from the C1 structures, the number of the Raman bands enhances, as the number of formula units in the unit cell increases. The modification from an “albite-like” Raman spectrum to a more “anorthite-like” spectrum occurs from sample An78 onwards, which coincides with the appearance of c reflections in the diffraction patterns of the samples. The evolution of the Raman bands υa and υb displays two changes in slope at ~An45 and ~An75: the first one occurs between e2 and e1 plagioclases, the latter separates e1 and I1 plagioclases with only b reflections in their diffraction patterns from I1 and P1 samples having b and c reflections too. The first variation represents exactly the e2→e1 phase transitions, whereas the second one corresponds in good approximation to the C1→I1 transition, which has been determined at ~An70 by previous works. The I1→P1 phase transition in the anorthite-rich side of the solid solution is not highlighted in the collected Raman spectra. Variations in peak broadening provide insights into the behaviour of the order parameter on a local scale, suggesting an increase in the structural disorder within the solid solution, as the structures have to incorporate more Al atoms to balance the change from monovalent to divalent cations. All the information acquired on these natural plagioclases has been used to produce a protocol able to give a preliminary estimation of the chemical composition of an unknown plagioclase from its Raman spectrum. Two calibration curves, one for albite-rich plagioclases and the other one for the anorthite-rich plagioclases, have been proposed by relating the peak linewidth of the most intense Raman band υa and the An content. It has been pointed out that the dependence of the composition from the linewidth can be obtained only for low structural plagioclases with a degree of order not far away from the references. The proposed tool has been tested on three mineralogical samples, two of meteoric origin and one of volcanic origin. Chemical compositions by Raman spectroscopy compare well, within an error of about 10%, with those obtained by elemental techniques. Further analyses on plagioclases with unknown composition will be necessary to validate the suggested method and introduce it as routine tool for the determination of the chemical composition from Raman data in planetary missions.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

Toward an atomistic understanding of the immune synapse:large-scale molecular dynamics simulation of a membrane-embedded TCR-pMHC-CD4 complex

T-cell activation requires interaction of T-cell receptors (TCR) with peptide epitopes bound by major histocompatibility complex (MHC) proteins. This interaction occurs at a special cell-cell junction known as the immune or immunological synapse. Fluorescence microscopy has shown that the interplay among one agonist peptide-MHC (pMHC), one TCR and one CD4 provides the minimum complexity needed to trigger transient calcium signalling. We describe a computational approach to the study of the immune synapse. Using molecular dynamics simulation, we report here on a study of the smallest viable model, a TCR-pMHC-CD4 complex in a membrane environment. The computed structural and thermodynamic properties are in fair agreement with experiment. A number of biomolecules participate in the formation of the immunological synapse. Multi-scale molecular dynamics simulations may be the best opportunity we have to reach a full understanding of this remarkable supra-macromolecular event at a cell-cell junction.

Stock market efficiency before and after a financial liberalisation reform:do breaks in volatility dynamics matter?

This article focuses on the deviations from normality of stock returns before and after a financial liberalisation reform, and shows the extent to which inference based on statistical measures of stock market efficiency can be affected by not controlling for breaks. Drawing from recent advances in the econometrics of structural change, it compares the distribution of the returns of five East Asian emerging markets when breaks in the mean and variance are either (i) imposed using certain official liberalisation dates or (ii) detected non-parametrically using a data-driven procedure. The results suggest that measuring deviations from normality of stock returns with no provision for potentially existing breaks incorporates substantial bias. This is likely to severely affect any inference based on the corresponding descriptive or test statistics.

G-protein-coupled receptors:from structural insights to functional mechanisms

The papers resulting from the recent Biochemical Society Focused Meeting 'G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms' held in Prato in September 2012 are introduced in the present overview. A number of future goals for GPCR (G-protein-coupled receptor) research are considered, including the need to develop biophysical and computational methods to explore the full range of GPCR conformations and their dynamics, the need to develop methods to take this into account for drug discovery and the importance of relating observations on isolated receptors or receptors expressed in model systems to receptor function in vivo. © 2013 Biochemical Society.

Bridging large and small scales of water models using hybrid Molecular Dynamics/Fluctuating Hydrodynamics framework

This thesis presents a two-dimensional water model investigation and development of a multiscale method for the modelling of large systems, such as virus in water or peptide immersed in the solvent. We have implemented a two-dimensional ‘Mercedes Benz’ (MB) or BN2D water model using Molecular Dynamics. We have studied its dynamical and structural properties dependence on the model’s parameters. For the first time we derived formulas to calculate thermodynamic properties of the MB model in the microcanonical (NVE) ensemble. We also derived equations of motion in the isothermal–isobaric (NPT) ensemble. We have analysed the rotational degree of freedom of the model in both ensembles. We have developed and implemented a self-consistent multiscale method, which is able to communicate micro- and macro- scales. This multiscale method assumes, that matter consists of the two phases. One phase is related to micro- and the other to macroscale. We simulate the macro scale using Landau Lifshitz-Fluctuating Hydrodynamics, while we describe the microscale using Molecular Dynamics. We have demonstrated that the communication between the disparate scales is possible without introduction of fictitious interface or approximations which reduce the accuracy of the information exchange between the scales. We have investigated control parameters, which were introduced to control the contribution of each phases to the matter behaviour. We have shown, that microscales inherit dynamical properties of the macroscales and vice versa, depending on the concentration of each phase. We have shown, that Radial Distribution Function is not altered and velocity autocorrelation functions are gradually transformed, from Molecular Dynamics to Fluctuating Hydrodynamics description, when phase balance is changed. In this work we test our multiscale method for the liquid argon, BN2D and SPC/E water models. For the SPC/E water model we investigate microscale fluctuations which are computed using advanced mapping technique of the small scales to the large scales, which was developed by Voulgarakisand et. al.

Molecular Dynamics implementation of BN2D or 'Mercedes Benz' water model

Two-dimensional 'Mercedes Benz' (MB) or BN2D water model (Naim, 1971) is implemented in Molecular Dynamics. It is known that the MB model can capture abnormal properties of real water (high heat capacity, minima of pressure and isothermal compressibility, negative thermal expansion coefficient) (Silverstein et al., 1998). In this work formulas for calculating the thermodynamic, structural and dynamic properties in microcanonical (NVE) and isothermal-isobaric (NPT) ensembles for the model from Molecular Dynamics simulation are derived and verified against known Monte Carlo results. The convergence of the thermodynamic properties and the system's numerical stability are investigated. The results qualitatively reproduce the peculiarities of real water making the model a visually convenient tool that also requires less computational resources, thus allowing simulations of large (hydrodynamic scale) molecular systems. We provide the open source code written in C/C++ for the BN2D water model implementation using Molecular Dynamics.

Applied Aspects of Mathematical Modeling and Optimization of Dynamics of Charged Beams

The complex of questions connected with the analysis, estimation and structural-parametrical optimization of dynamic system is considered in this article. Connection of such problems with tasks of control by beams of trajectories is emphasized. The special attention is concentrated on the review and analysis of spent scientific researches, the attention is stressed to their constructability and applied directedness. Efficiency of the developed algorithmic and software is demonstrated on the tasks of modeling and optimization of output beam characteristics in linear resonance accelerators.