Dissipative particle dynamics simulation of a gold nanoparticle system

Dissipative particle dynamics (DPD) was carried out to study systems containing gold atoms, organic ether (oligohydroquinonyl ether terminated with a thiol group) and organic solvents. The components in the simulated system are very different in size and chemical nature. Our simulation showed that the reproduction of the macroscopic experimental phase separation, properly dividing the polymeric molecule into beads, selecting the size of gold bead, and choosing the appropriate interaction parameters between beads are crucial. In addition, the solvent effect was the dominant factor for the formation of spherical aggregates of Au atoms and organic ether molecules. We report the interaction strengths between the solvent and gold clusters. Our work has demonstrated that DPD methods can be applied to the study of complex meso-scale systems.     

Cross-Scale Numerical Simulations Using Discrete Particle Models

Abstract

We propose a concept for a homogenous computational model in carrying out cross-scale numerical experiments on liquids. The model employs the particle paradigm and comprises three types of simulation techniques: molecular dynamics (MD), dissipative particle dynamics (DPD) and smoothed particle hydrodynamics (SPH). With respect to the definition of the collision operator, this model may work in different hierarchical spatial and time scales as: MD in the atomistic scale, DPD in the mesoscale and SPH in the macroscale. The optimal computational efficiency of the three types of cross-scale experiments are estimated in dependence on: the system size N-where N is the number of particles-and the number of processors P employed for computer simulation. For the three-hierarchical-stage, as embodied in the MD-DPD-SPH model, the efficiency is proportional to N ^8/7 but its dependence on P is different for each of the three types of cross-scale experiments. The problem of matching the different scales is discussed.     

Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method

Restrained and unrestrained aqueous solution molecular dynamics simulations applying the particle mesh Ewald (PME) method to DNA duplex structures previously determined via in vacuo restrained molecular dynamics with NMR-derived restraints are reported. Without experimental restraints, the DNA decamer, d(CATTTGCATC)d(GATGCAAATG) and trisdecamer, d(AGCTTGCCTTGAG)d(CTCAAGGCAAGCT), structures are stable on the nanosecond time scale and adopt conformations in the B-DNA family. These free DNA simulations exhibit behavior characteristic of PME simulations previously performed on DNA sequences, including a low helical twist, frequent sugar pucker transitions, BI- BII(–) transitions and coupled crankshaft (–) motion. Refinement protocols similar to the original in vacuo restrained molecular dynamics (RMD) refinements but in aqueous solution using the Cornell et al. force field [Cornell et al. (1995) J. Am. Chem. Soc., 117, 5179–5197] and a particle mesh Ewald treatment produce structures which fit the restraints very well and are very similar to the original in vacuo NMR structure, except for a significant difference in the average helical twist. Figures of merit for the average structure found in the RMD PME decamer simulations in solution are equivalent to the original in vacuo NMR structure while the figures of merit for the free MD simulations are significantly higher. The free MD simulations with the PME method, however, lead to some sequence-dependent structural features in common with the NMR structures, unlike free MD calculations with earlier force fields and protocols. There is some suggestion that the improved handling of electrostatics by PME improves long-range structural aspects which are not well defined by the short-range nature of NMR restraints.     

Molecular dynamics as a tool to help design mutants

A 200 ps MD trajectory of wild type PCI and a 120 ps one for the Pro36Gly putative mutant are studied and compared with the structure of PCI in its complex with carboxypeptidase A (CPA). It is first established that the structures of PCI from X-ray and from MD simulation are essentially equal. Thereafter, data from the PCI-CPA and average MD structures together with available biochemical information are used to identify possible structural factors that may determine the inhibitory power of PCI. These structural determinants are used to analyze the mutant structure. The fold of the mutant protein shows a large degree of stability. The N-terminal tail in PCIm differs from the X-ray structure as it does in PCIw, while the mutant's C-terminal tail (which is the primary binding site with CPA) and residues 13–17 present deviations. Differences in fluctuation patterns exist between PCIm and PCIw in residues 2–4 (the N-terminal tail), 13–17, 22–23, 28–81 (the secondary contact site with CPA), and 37–38 (the C-terminal tail); the latter region is rigidified in PCIm. Results show that the MD method is able to sense long-range as well as local perturbative effects produced by amino-acid substitutions in flexible regions of this protein. The simulations suggest that the conformation of the C-terminal tail is less favorable for interaction with the target protein in the mutant than it is in the wild type protein. The Pro-36-Gly mutant is predicted to be a less potent inhibitor.Abbreviations CPA carboxypeptidase A - MD molecular dynamics - NIS non-inertial solvent - PCI potato carboxypeptidase A inhibitor - PCIm mutated inhibitor - PCIw wild inhibitor     

Predicting rheology of suspensions of spherical and non-spherical particles using dissipative particle dynamics (DPD): methodology and experimental validation

The rheology of non-dilute colloidal suspensions is a complex phenomenon and predictive numerical methodologies for it are still in the emerging phases. Dissipative particle dynamics (DPD), a particle-based numerical scheme for phenomena in the mesoscopic regime, has emerged as an attractive technique to tackle this problem. In this article, a practical methodology for using DPD for quantitative prediction of the rheology of non-dilute suspensions is presented and validated with focused, specific experiments. Some pertinent issues are highlighted to make DPD more amenable to being a computational tool for practical applications. The presence of solid particles of disparate sizes and non-spherical geometries poses special challenges. Methodologies to address them are presented with validations and efficient techniques are suggested to make them computationally amenable.     

Structural analysis of telechelic polymer solution using dissipative particle dynamics simulations

A telechelic polymer is an amphiphilic polymer that can form micellar structures when dissolved in water. A telechelic polymer solution shows viscoelastic behaviour owing to the formation of characteristic networks, i.e. loops, bridges and dangling chains. For industrial purposes, telechelic polymers have many applications as thickening agents, such as in paints and cosmetics. Thus, it is desirable to predict and control the rheological properties of telechelic polymers. However, detailed studies at the molecular level have not yet been performed. In this study, I use the dissipative particle dynamics (DPD) method to investigate the relationship between the characteristic structural properties and the molecular structure in telechelic polymer solutions. I show that the morphology of telechelic polymer solutions depends on the concentration and chain length, the distribution of the end-to-end distance, the mean square end-to-end distance, the mean square radius of gyration and the time-averaged mean square displacement. Although an effect of entanglement is important for properties of polymer melts, the polymer chain composed of DPD particles cannot reproduce it. Therefore, I compare telechelic polymer solutions with and without the segmental repulsive potential (SRP), which can simulate the effect of entanglement in DPD simulations. The results indicate that it is necessary to include the SRP in DPD simulations to correctly analyse the behaviour of telechelic polymer solutions.     

Lees–Edwards boundary condition for simulation of polymer suspension with dissipative particle dynamics method

The Lees–Edwards boundary condition (LEbc) is widely used in particle-based simulation for producing shear flow. Application of traditional LEbc in dissipative particle dynamics (DPD) method may encounter certain problems, e.g. it will destroy the momentum conservation law at the near boundary region, and the coordinate system gives an incorrect end-to-end vector for polymer beads. Special treatments of the implementation of LEbc in DPD method are introduced in this paper. A single side ghost layer is used to keep the momentum conservation, and the global coordinate system is employed to obtain a correct calculation of the spring force between polymer beads. The simulation results give a good prediction of velocity profile and system temperature, and the elastic dumbbell model for current method can well represent the Oldroyd-B fluid.     

Heat transfer simulation using energy conservative dissipative particle dynamics

Dissipative particle dynamics with energy conservation (eDPD) was used to investigate conduction heat transfer in two dimensions under steady-state condition. Various types of boundary condition were implemented to the conduction domain. Besides, 2D conduction with internal heat generation was studied and the heat generation term was used to measure the thermal conductivity and diffusivity of the eDPD system. The boundary conditions used include both the Neumann and Dirichlet boundary conditions. The Neumann boundary condition was applied via adiabatic surfaces and surfaces exposed to convection heat transfer. The DPD simulations were compared to analytical solutions and finite-difference techniques. It was found that DPD appropriately predicts the temperature distribution in the conduction regime. Details of boundary condition implementation and thermal diffusivity measurement are also described in this paper.     

Study of the stability of long-range-ordered lamellar structures for directed self-assembly lithography,performed using dissipative particle dynamics

We performed dissipative particle dynamics (DPD) simulations to obtain long-range-ordered lamellar structures for directed self-assembly lithography. The self-assembled structure of diblock copolymers (DBCs) depends on the length of the different blocks and the difference in their solubility parameters. In the DPD simulations, the DBCs were formed from coarse-grained particles, and the difference between the solubility parameters was represented by a repulsion parameter. We examined the phase separation morphology of the DBCs, which were confined using a trench model system. The repulsion parameter for the assembly of the lamellar structures from the DBC particles was chosen from six types of parameters. The orientation of the lamellar structure was controlled by the repulsion parameter that described the repulsion between the particles and the wall of the system. We changed the width of the trench, and examined the probability for the formation of the lamellar structure. The lamellar structure could not be obtained by increasing the width. To increase the probability, we placed a ridge at the centre of the bottom wall. It was found that the presence of the ridge increased the probability for the formation of the long-range-ordered lamellar structures.     

Spontaneous self-assembly of diblock copolymers in nanoconfined geometries by dissipative particle dynamics

We performed dissipative particle dynamics (DPD) simulations to reproduce phase separation morphologies of diblock copolymers for directed self-assembly (DSA) lithography. DSA is a promising technique to overcome the current photolithography resolution limit. The Flory–Huggins χ parameter estimated from a small-angle X-ray scattering experiment was used for the DPD simulations owing to the multiple degrees of coarse-graining. The degree of coarse-graining and the bond parameter for the spring force were optimised to represent the experimental result of the number of lamellar layers formed in a trench guide. The DPD simulations using these parameters can also represent the diameter of the central cylinder domain that is formed by phase separation in the cylindrical hole. It was found that the bond parameter considering the spreading of polymer segments in a coarse-grained particle gives good quantitative agreement between the results of the simulations and the experimental data.     

Molecular dynamics and dissipative particle dynamics simulations for prediction of miscibility in polyethylene terephthalate/polylactide blends

The miscibility of polyethylene terephthalate (PET)/polylactide (PLA) blends is studied through atomistic molecular dynamics (MD) and mesoscale dissipative particle dynamics (DPD) simulation. Five PET/PLA blends (with the weight ratio at 90/10, 70/30, 50/50, 30/70 and 10/90) as well as pure PET and PLA are examined. The solubility parameter values obtained by using the MD simulation are in good agreement with the reference data. The Flory–Huggins parameters, χ, which are computed for different blends and determined from the cohesive energy densities, with the radial distribution functions g(r) of the inter-molecular atoms, suggest that PET is completely miscible with PLA over the entire composition range. This is further proved by the mesoscopic morphologies of PET/PLA blends. All the simulation results are qualitatively consistent with the experimental results, and demonstrate that the modelling strategies in this study may serve as a powerful tool for predicting miscibility and mesoscopic morphology of polymer blends.     

Scaling behaviour of different polymer models in dissipative particle dynamics of unentangled melts

We present a dissipative particle dynamics (DPD) study of scaling behaviour for three polymer models. The scaling behaviour is explored for the conformational and dynamic properties of unentangled polymer melts. DPD employs a bead–spring model together with an aggressive coarse-graining to represent polymers at the mesoscale. The first model studied utilises a simple soft repulsion potential for the bead–bead interactions together with a harmonic spring potential to connect beads into a polymer chain. The second model differs from the first model by replacing the harmonic spring with a finitely extensible nonlinear elastic spring. The third model uses realistic coarse-grain potentials for the bead–bead, spring and bending interactions based on the iterative Boltzmann inversion procedure and it corresponds to a mesoscopic model of polyethylene. We systematically vary the chain length and spring constant (in the case of the first and second models), and simulate the conformational properties such as the end-to-end distance or radius of gyration, and dynamic properties such as the centre-of-mass self-diffusion coefficient or viscosity. The scaling of the conformational and dynamic properties with chain length (scaling laws) is compared with the Rouse theory, which is considered as a standard theory for unentangled polymer melts. The comparison shows that simulated scaling laws typically agree with the Rouse scaling laws for the DPD polymer models with more than 10 DPD beads. For the shorter DPD polymers, deviations from the Rouse theory exist and become significant for the dynamic properties, especially for the viscosity of the polymer melts.     

A study of collective atomic fluctuations and cooperativity in the U1A-RNA complex based on molecular dynamics simulations

Cooperative interactions play an important role in recognition and binding in macromolecular systems. In this study, we find that cross-correlated atomic fluctuations can be used to identify cooperative networks in a protein–RNA system. The dynamics of the RRM-containing protein U1A–stem loop 2 RNA complex have been calculated theoretically from a 10 ns molecular dynamics (MD) simulation. The simulation was analyzed by calculating the covariance matrix of all atomic fluctuations. These matrix elements are then presented in the form of a two-dimensional grid, which displays fluctuations on a per residue basis. The results indicate the presence of strong, selective cross-correlated fluctuations throughout the RRM in U1A–RNA. The atomic fluctuations correspond well with previous biophysical studies in which a multiplicity of cooperative networks have been reported and indicate that the various networks identified in separate individual experiments are fluctuationally correlated into a hyper-network encompassing most of the RRM. The calculated results also correspond well with independent results from a statistical covariance analysis of 330 aligned RRM sequences. This method has significant implications as a predictive tool regarding cooperativity in the protein–nucleic acid recognition process.     

Implicit solvent model estimates of the stability of model structures of the alamethicin channel

Alamethicin is a hydrophobic helical peptide of 20 residues, which oligomerizes to form ion-conducting channels in membranes. The behavior of an intact alamethicin channel in POPC bilayers was recently studied, using 2 ns molecular dynamics (MD) simulations of a model hexameric channel. These simulations produced numerous conformations of the channel. In the present study, we used 11 of these channel conformations and carried out continuum-solvent model calculations, similar to those used for the monomers in our previous studies, to investigate the energetics of the channel inside the lipid bilayer. Our results suggest that, out of the 11 channel conformations produced by the MD simulations, only four are stable inside the lipid bilayer, with water-to-membrane free energies of transfer ranging from ~–6 to ~–10 kcal/mol. Analysis of the results suggests two causes for the apparent instability of the remainder of the structures inside the lipid bilayer, both resulting from the desolvation of channel polar groups (i.e. their transfer from the aqueous phase into the bilayer). The first is specific, uncompensated backbone hydrogen bonds, which exist in the region of the channel exposed to the hydrocarbon of the lipid bilayer. The second is exposure of intra-pore water molecules to the surrounding lipid. Thus, the association of these structures with the membrane involves a large electrostatic desolvation free-energy penalty. The apparent conflict between continuum-solvent and MD calculations, and its significance for the interpretation of membrane proteins simulations, are discussed.     

Molecular dynamics simulation of oleyl oleate swollen micelles system

Problems with transdermal drug delivery were directly associated with the skin barrier which is the lipid bilayer at the stratum corneum. Chemical penetration enhancers such as swollen micelles that formed from the solubilisation of the surfactants in the nano-emulsion system could provide an effective solution. However, the structural properties of swollen micelles from nano-emulsions of palm-oil esters, whose behaviour is related to colloidal systems, have not been studied in great detail. In this paper, we report on the use of molecular dynamics (MD) simulations to investigate the structural properties of swollen micelles of oleyl oleate (OE). Five series of 10 ns MD simulations were performed at different micelle compositions to determine the structural evolution of OE/Span20 (S20) swollen micelles. We also carried out four MD simulations on the structure of S20, OE/S20, Tween80 (T80) and OE/T80 micelles to study the effect of different surfactants and the addition of OE into the systems. The shapes of the swollen micelles were observed to vary by the difference in the micelle composition, the surfactants used and the addition of OE. The results were correlated with published theory, and consistent with experimental results on the phase behaviour of the nano-emulsion system.     

Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the guanine-nucleotide exchange protein, SOS, identified from molecular dynamics calculations. Selective inhibition of oncogenic ras-p21

In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras–p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631–641, 676–691, 718–729, and 994–1004, which differ in structure between the two complexes. We have now microinjected synthetic peptides corresponding to each of these domains into Xenopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oocytes subsequently incubated with insulin. We find that the first three peptides inhibit both oncogenic and wild-type p21-induced oocyte maturation, while the last peptide much more strongly inhibits oncogenic p21 protein-induced oocyte maturation. These results suggest that each identified SOS region is involved in ras–stimulated signal transduction and that the 994–1004 domain is involved uniquely with oncogenic ras–p21 signaling.     

Identification, using molecular dynamics, of an effector domain of the ras-binding domain of the raf-p74 protein that is uniquely involved in oncogenic ras-p21 signaling

By comparing the average structures, computed using molecular dynamics, of the ras-binding domain of raf (RBD) bound to activated wild-type ras-p21 and its homologous inhibitory protein, rap-1A, we formerly identified three domains of the RBD that changed conformation between the two complexes, residues 62–76, 97–110, and 111–121. We found that one synthetic peptide, corresponding to RBD residues 97–110, selectively inhibited oncogenic ras-p21-induced oocyte maturation. In this study, we performed molecular dynamics on the Val 12-ras-p21-RBD complex and compared its average structure with that for the wild-type protein. We find that there is a large displacement of a loop involving these residues when the structures of the two complexes are compared. This result corroborates our former finding that the RBD 97–110 peptide inhibits only signal transduction by oncogenic ras-p21 and suggests that oncogenic p21 uses this loop to interact with raf in a unique manner.     

Sequence dependence of amyloid fibril formation: insights from molecular dynamics simulations

The clarification of the physico-chemical determinants underlying amyloid deposition is critical for our understanding of misfolding diseases. With this purpose we have performed a systematic all-atom molecular dynamics (MD) study of a series of single point mutants of the de novo designed amyloidogenic peptide STVIIE. Sixteen different 50ns long simulations using explicit solvent have been carried out starting from four different conformations of a polymeric six-stranded beta-sheet. The simulations have provided evidence for the influence of a small number of site-specific hydrophobic interactions on the packing and stabilization of nascent aggregates, as well as the interplay between side-chain interactions and the net charge of the molecule on the strand arrangement of polymeric beta-sheets. This MD analysis has also shed light into the origin of the position dependence on mutation of beta-sheet polymerization that was found experimentally for this model system. Our results suggest that MD can be applied to detect critical positions for beta-sheet aggregation within a given amyloidogenic stretch. Studies similar to the one presented here can guide site-directed mutations or the design of drugs that specifically disrupt the key stabilizing interactions of beta-sheet aggregates.