Multiscale Simulation Study Research Articles

Photocurrent contribution from inter-segmental mixing in donor–acceptor-type polymer solar cells: A multiscale simulation study

Polymer solar cells possess a promising perspective for generating renewable energy at affordable costs, provided their performance and durability can be improved considerably. To this end, several experimental and theoretical techniques have been devised recently, establishing a direct link between local morphology, local opto-electronic properties and device performance. However, their reliability is still unclear to this day. Here, we demonstrate by using a recently developed particle-based multiscale solar cell approach and comparing its results with the ones of a field-based solar cell algorithm that inter-mixing of the electron-donor(D)- and -acceptor(A)-type of segments in a lamellar-like poly(9,9’-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylene-diamine)-poly(9,9'-dioctylfluorene-co-benzothiadiazole) (PFB-F8BT) blend causes that the major part of the charge generation and charge transport takes place inside the nanophases of the nanostructured polymer solar cells in agreement with recent experimental measurements and not, as commonly believed, at the visible domain boundaries of the DA interface. Moreover, we show that the contribution of the exciton dissociation efficiency to the internal quantum efficiency, due to inter-monomeric mixing, is significant and cannot be neglected in simulation studies at the nanoscale. Finally, we demonstrate that keto-defects on the fluorene moiety of the F8BT phase, induced by photo-oxidation, causes a simultaneous increase of the intra-chain contribution and decrease of the inter-chain contribution to the electronic current density, whereas in the reduced form the difference between both contributions is significantly smaller. This antagonistic effect leads to keto-induced electron trapping, resulting in a deteriorated electronic transport efficiency in devices with a photo-oxidized F8BT phase.

Specific DNA Sequence Search Dynamics of p53 and Effect of Acetylation of its C-Terminal Domain: Multi-Scale Simulation Study

A transcription factor p53 is composed of ordered Core and Teramerization domain and of intrinsically disordered N-terminal domain, C-terminal domain and the linker region, which prevent to elucidate the functional mechanism based on static structural analyses. In order to model the linker region supposed to play an important role, first, we performed all atom (AA) multi-canonical MD simulation of this 40 amino acid residues long region. Second, we decided the parameters of CG model so that the contact map of the CG structural ensemble was marginally same as that from the AA simulation. The SAXS profile obtained from the CG simulation using these parameters reproduces the previous experiment. Finally, we conducted the CG simulation of the system containing a full-length p53 quaternary structure and a 100 bp DNA including a p53 binding site. In the production simulation, p53 spontaneously binds to its binding site and forms a complex structure that is consistent with the electron microscopic model obtained previously. The result also revealed that p53 slides along nonspecific dsDNA with its CTD before it binds to REs, whereas, upon acetylation of the CTD, it repeats dissociation from and association to dsDNA, suggesting that previously suggested inhibitory effect of the CTD on binding of p53 to its binding site and the nullification of the inhibitory effect upon acetylation are largely attributed to the change of main search mechanism from sliding to 3D diffusion. Taken together, the result of this multi-scale simulation shed light on the problem that is difficult for conventional experimental technique to address due to the flexibility of this protein.

An efficient and cyclic hydrogen evolution reaction mechanism on [Ni(PH2NH2)2]2+ catalysts: a theoretical and multiscale simulation study

In this paper we report a theoretical and a multiscale simulation study of the hydrogen evolution reaction (HER) on the [Ni(PH2NH2)2]2+ catalyst in acidic media (2H+ + 2e− → H2). First, at the DFT calculations level, a cyclic pathway for the HER is proposed highlighting the shuttling of electrons with protons on the conformationally flexible catalyst. The theoretical calculation gives a better understanding of the efficient cyclic pathway of [Ni(PH2NH2)2]2+, and the effect of solvent on the mechanism has been discussed. The σ-donating and π-accepting nature of H2–Ni bond has been identified in the H2 complex. The oxidation state of the Ni centre and geometrical changes of the catalyst in the reaction coordinate are also identified. Then a mean-field kinetic model incorporating the calculated DFT data has been developed. This model allows us to simulate the behaviour of these catalysts in electrochemical conditions representative of polymer electrolyte membrane water electrolyzers operation. Calculated results include experimental observables such as polarization curves showing good agreement with available experimental data. Competitive phenomena between the different electrochemical mechanisms, the protons and H2 transport, and their relative impact on the overall cell performance are particularly discussed.

The thermosetting resin prepared by curing reaction of typical soybean oil and properties of the product network structures: a multiscale simulation study

With our multiscale simulation strategy developed previously, we study the curing reaction of soybean oil and styrene to prepare a thermosetting resin. From atomistic simulation details, we estimate the parameters used in coarse-grained (CG) simulations. Then, with the mesoscopic dissipative particle dynamics simulation, the CG network structure and average cross-linking density of a material can be obtained. Finally, the reverse-mapping scheme of the CG structure to atomistic representation is carried out to analyse the mechanical properties and the glass transition temperature of the system. We find in such a system that the molar ratio of double bonds in the two reactants plays a significant role in determining the physical properties of a product. These results shed light on improved control and design of thermosetting resin material via curing reaction of soybean oil.

3P118 転写因子p53の特異的結合部位探索・認識機構 : マルチスケールシミュレーション研究(04.核酸結合蛋白質,ポスター,日本生物物理学会年会第51回(2013年度))

3P118 転写因子p53の特異的結合部位探索・認識機構 : マルチスケールシミュレーション研究(04.核酸結合蛋白質,ポスター,日本生物物理学会年会第51回(2013年度))

Molecular basis of calcium-sensitizing and desensitizing mutations of the human cardiac troponin C regulatory domain: a multi-scale simulation study.

Troponin C (TnC) is implicated in the initiation of myocyte contraction via binding of cytosolic and subsequent recognition of the Troponin I switch peptide. Mutations of the cardiac TnC N-terminal regulatory domain have been shown to alter both calcium binding and myofilament force generation. We have performed molecular dynamics simulations of engineered TnC variants that increase or decrease sensitivity, in order to understand the structural basis of their impact on TnC function. We will use the distinction for mutants that are associated with increased affinity and for those mutants with reduced affinity. Our studies demonstrate that for GOF mutants V44Q and L48Q, the structure of the physiologically-active site II binding site in the -free (apo) state closely resembled the -bound (holo) state. In contrast, site II is very labile for LOF mutants E40A and V79Q in the apo form and bears little resemblance with the holo conformation. We hypothesize that these phenomena contribute to the increased association rate, , for the GOF mutants relative to LOF. Furthermore, we observe significant positive and negative positional correlations between helices in the GOF holo mutants that are not found in the LOF mutants. We anticipate these correlations may contribute either directly to affinity or indirectly through TnI association. Our observations based on the structure and dynamics of mutant TnC provide rationale for binding trends observed in GOF and LOF mutants and will guide the development of inotropic drugs that target TnC.

PH-sensitive drug loading/releasing in amphiphilic copolymer PAE–PEG: Integrating molecular dynamics and dissipative particle dynamics simulations

Molecular dynamics (MD) and dissipative particle dynamics (DPD) simulations are integrated to investigate the loading/releasing of anti-cancer drug camptothecin (CPT) in pH-sensitive amphiphilic copolymer, composed of hydrophobic poly(β-amino ester) (PAE) and hydrophilic methyl ether-capped poly(ethylene glycol) (PEG). MD simulation is used to estimate the Flory–Huggins interaction parameters and miscibility of binary components. On this basis, DPD simulation is applied to examine the micellization of PAE–PEG, CPT loading in PAE–PEG, and CPT releasing in PAEH–PEG. With increasing concentration, PAE–PEG forms spherical then disk-like micelles and finally vesicles, as a competitive counterbalance of free energies for the formation of shell, interface and core. CPT loading in PAE–PEG micelles/vesicles is governed by adsorption-growth-micellization mechanism, and CPT is loaded into both hydrophobic core and interface of hydrophobic core/hydrophilic shell. The predicted loading efficiency is close to experimental value. Similar to literature reports, the loading of high concentration of CPT is observed to cause morphology transition from micelles to vesicles. Upon protonation, CPT is released from micelles/vesicles by swelling-demicellization-releasing mechanism. This multi-scale simulation study provides microscopic insight into the mechanisms of drug loading and releasing, and might be useful for the design of new materials for high-efficacy drug delivery.

Effect of secondary structure on the self-assembly of amphiphilic molecules: A multiscale simulation study

The self-assembly of amphiphilic molecules is of interest from a fundamental and practical standpoint. There has been recent interest in a class of molecules made from β-amino acids (which contain an additional backbone carbon atom when compared with natural amino acids). Block copolymers of β-peptides, where one block is hydrophobic and the other is hydrophilic, self-assemble into micelles. In this work, we use computer simulations to provide insight into the effect of secondary structure on the self-assembly of these molecules. Atomistic simulations for the free energy of association of a pair of molecules show that a homochiral hydrophobic block promotes self assembly compared to a heterochiral hydrophobic block, consistent with experiment. Simulations of a coarse-grained model show that these molecules spontaneously form spherical micelles.

Molecular origin of differences in hole and electron mobility in amorphous Alq3—a multiscale simulation study

In order to determine the molecular origin of the difference in electron and hole mobilities of amorphous thin films of Alq(3) (meridional Alq(3) (tris(8-hydroxyquinoline) aluminium)) we performed multiscale simulations covering quantum mechanics, molecular mechanics and lattice models. The study includes realistic disordered morphologies, polarized site energies to describe diagonal disorder, quantum chemically calculated transfer integrals for the off-diagonal disorder, inner sphere reorganization energies and an approximative scheme for outer sphere reorganization energies. Intermolecular transfer rates were calculated via Marcus-theory and mobilities were simulated via kinetic Monte Carlo simulations and by a Master Equation approach. The difference in electron and hole mobility originates from the different localization of charge density in the radical anion (more delocalized) compared to the radical cation (more confined). This results in higher diagonal disorder for holes and less favourable overlap properties for the hole transfer integrals leading to an overall higher electron mobility.

Protecting Bacterial Cells from Rupture: A Multiscale Simulation Study of Braun's Lipoprotein

The cell envelope of Gram-negative bacteria is composed of two membranes. The inner membrane has a relatively simple phospholipid composition, whilst the asymmetric outer membrane is a complex mixture of lipopolysaccharide (LPS) and phospholipids. The region between the two membranes, know as the periplasm, is largely composed of peptidoglycan that maintains the cell shape and protects its from rupture. Braun's lipoprotein (BLP), a coiled-coiled trimeric protein located within the periplasm, has long been known to covalently bind to the peptidoglycan and to anchor the peptidoglycan to the inner leaflet of the outer membrane. Recently, however, it has been shown that in addition to this structural role, BLP is able to adopt a trans-membrane orientation across the outer membrane.In this present study we have performed a series of molecular dynamics simulations of BLP using both atomistic and coarse-grained approaches. An atomistic model of the peptidoglycan has been developed and incorporated with our complex model of the E. coli outer membrane that contains LPS in the outer leaflet and mixtures of phospholipids in the inner leaflet. Multiple simulations of BLP, including the peptidoglycan bound and free forms, plus BLP in a trans-membrane orientation have been performed. These simulations have enabled us to explore the conformational dynamics, oligomerisation and environmental interactions of BLP in these different orientations.

Multiscale Simulation and Experimental Study of Novel SiC Structured Packings

Two SiC corrugated structured packings are developed: one being smooth plate and the other made of porous SiC foam. Accordingly, a macroscale three-dimensional (3D) geometric module of two corrugated sheets is introduced with a periodic boundary and a microscale computational geometry is gained from arrayed tetrakaidecahedrons. Single-phase modeling is carried out in the macro module to determine the dry pressure drops for the two types of packing. The results show that the porous SiC packing has a higher pressure drop than that of the smooth one. Two-phase flow for smooth packing is simulated with a VOF-like model provided by CFX in the macroscale geometry. It is found that openings in corrugated plates can improve the film distribution and mass-transfer efficiency. Microsimulation of two-phase flow in the porous SiC packing is performed, and the results prove that liquid can go inside the SiC foam and extend along the foam matrix with a velocity. Therefore, the porous foam can provide a larger effective gas-liquid interfacial area for mass transfer, which explains its larger theoretical plate number, compared to the smooth packing. Performance parameters including pressure drop and liquid holdup have been measured to validate the simulation method, while the distillation experiments have been carried out to study the mass-transfer efficiency of the novel SiC packings.

Multiscale Simulation Study on the Curing Reaction and the Network Structure in a Typical Epoxy System

We propose a multiscale simulation strategy to study the interplay between diffusion and curing reaction on the network formation and the corresponding mechanical properties of epoxy resins. Atomistic molecular dynamics simulations are first used to estimate the parameters that will be used in coarse-grained simulations. Then a dissipative particle dynamics coupled with curing reaction model is developed and adopted to simulate the cross-linking process of the system to form an epoxy network structure. We find that, during the curing process, to which extent that the components can diffuse between each other greatly influences the generated network structure. Finally, the reverse mapping of the coarse-grained structure to atomistic representation is carried out to analyze the mechanical properties and the Tg of the epoxy resin system.

The Binding Process of a Nonspecific Enzyme with DNA

Protein-DNA recognition of a nonspecific complex is modeled to understand the nature of the transient encounter states. We consider the structural and energetic features and the role of water in the DNA grooves in the process of protein-DNA recognition. Here we have used the nuclease domain of colicin E7 (N-ColE7) from Escherichia coli in complex with a 12-bp DNA duplex as the model system to consider how a protein approaches, encounters, and associates with DNA. Multiscale simulation studies using Brownian dynamics and molecular-dynamics simulations were performed to provide the binding process on multiple length- and timescales. We define the encounter states and identified the spatial and orientational aspects. For the molecular length-scales, we used molecular-dynamics simulations. Several intermediate binding states were found, which have different positions and orientations of protein around DNA including major and minor groove orientations. The results show that the contact number and the hydrated interfacial area are measures that facilitate better understanding of sequence-independent protein-DNA binding landscapes and pathways.

Multiscale simulation of nanometric cutting of single crystal copper and its experimental validation

In this paper a multiscale simulation study was carried out in order to gain in-depth understanding of machining mechanism of nanometric cutting of single crystal copper. This study was focused on the effects of crystal orientation and cutting direction on the attainable machined surface quality. The machining mechanics was analyzed through cutting forces, chip formation morphology, generation and evolution of defects and residual stresses on the machined surface. The simulation results showed that the crystal orientation of the copper material and the cutting direction significantly influenced the deformation mechanism of the workpiece materials during the machining process. Relatively lower cutting forces were experienced while selecting crystal orientation family {111}. Dislocation movements were found to concentrate in front of the cutting chip while cutting on the (111) surface along the [1¯10] cutting direction thus, resulting in much smaller damaged layer on the machined surface, compared to other orientations. This crystal orientation and cutting direction therefore recommended for nanometric cutting of single crystal copper in practical applications. A nano-scratching experiment was performed to validate the above findings.

Microstructure-Based Modeling of Aging Mechanisms in Catalyst Layers of Polymer Electrolyte Fuel Cells

This work is comprised of a versatile multiscale modeling of carbon corrosion processes in catalyst layers (CLs) of polymer electrolyte fuel cells (PEFCs). Slow rates of electrocatalytic processes in CLs and materials aging are the main sources of voltage loss in PEFCs under realistic operating conditions. We combined microstructure data obtained from coarse-grained molecular dynamics (CGMD) simulations with a detailed description of the nanoscale elementary kinetic processes and electrochemical double-layer effects at the catalyst/electrolyte and carbon/electrolyte interfaces. We exclusively focused on morphology and microstructure changes in the catalyst layer of PEFCs as a result of carbon corrosion. By employing extensive CGMD simulations, we analyzed the microstructure of CLs as a function of carbon loss and in view of ionomer and water morphology, water and ionomer coverage, and overall changes in carbon surface. These ingredients are integrated into a kinetic model, which allows capture of the impact of the structural changes on the PEFC performance decay. In principle, such multiscale simulation studies allow a relation of the aging of CLs to the selection of carbon particles (sizes and wettability), the catalyst loading, and the level of ionomer structural changes during the CL degradation process.

Exploring the conformational dynamics and membrane interactions of PorB from C. glutamicum: A multi-scale molecular dynamics simulation study

Members of the gram-positive mycolata bacteria have unusual cell envelopes which help them to avoid the immune system and the effects of most antibiotics, whilst rendering them permeable to solutes of importance in industrial bioconversion. It is therefore of interest to understand the molecular mechanisms for this selective permeability. PorB is an unusual porin from the outer membrane (OM) of Corynebacterium glutamicum. It has been proposed as an atypical α-helical, symmetrical homo-pentameric architecture, with an unusual distribution of polar amino acids on its surface. The proposed structure is too short to traverse a typical phospholipid bilayer, in contrast with the β-barrel porins of Gram-negative bacteria. Nevertheless, it has been shown to form small anion-selective channels in membranes typical of Escherichia coli. To further understand its function, we have performed ~400ns of all-atom and ~270 μs of coarse-grained simulations of PorB in a range of membrane mimetic and phospholipid milieus. Our results suggest that PorB can undergo spontaneous conformational rearrangements that allow it to adapt to its local lipid environment. We speculate that the increased flexibility of this α-helical porin in comparison with rigid β-barrels may be an adaptation for the heterogeneous mycolic OM, and explains its demonstrated ability to form measurable pores with phospholipid membranes.

Structures and properties of PAMAM dendrimer: A multi-scale simulation study

Poly (amido-amine) (PAMAM) as one of the earliest synthesized dendrimers is now widely used in biomedicine, host–guest chemistry and so on. PAMAM dendrimers from generation 2 to 6 were studied by all-atom molecular dynamic simulations using different force fields and different coarse-graining schemes. The DREIDING force field is found to provide the best accuracy in predicting the structures and properties of PAMAM dendritic molecules. Simulation with the coarse-grained approach decreases the considerable CPU-time cost while keeping commensurate accuracy with all-atom simulations under the same simulation condition. The radius of gyration, solvent accessible surface area, solvent accessible volume and fractal dimension are calculated as functions of generation. Results show that PAMAM dendrimers have a fractal structure with dimensions between 2.0 and 3.0. The ample external terminal groups and internal voids make the PAMAM dendrimer an excellent candidate for drug carriers. The terminal groups of PAMAM dendrimers are sufficiently flexible to interpenetrate almost the whole molecule. The simulation results on different coarse-grained models are compared; the coarse-graining scheme has significant influence on the simulation accuracy.

Influence of poly(ethylene oxide) brushes on the rheological properties of MgO colloidal suspensions in water

A combined experimental and multiscale simulation study of the influence of polymer brush modification on interactions of colloidal particles and rheological properties of dense colloidal suspensions has been conducted. Our colloidal suspension is comprised of polydisperse MgO colloidal particles modified with poly(ethylene oxide) (PEO) brushes in water. The shear stress as a function of shear rate was determined experimentally and from multiscale simulations for a suspension of 0.48 volume fraction colloids at room temperature for both bare and PEO-modified MgO colloids. Bare MgO particles exhibited strong shear thinning behavior and a yield stress on the order of several Pascals in both experiments and simulations. In contrast, simulations of PEO-modified colloids revealed no significant yielding or shear thinning and viscosity only a few times larger than solvent viscosity. This behavior is inconsistent with results obtained from experiments where modification of colloids with PEO brushes formed by adsorption of PEO-based comb-branched chains resulted in relatively little change in suspension rheology compared to bare colloids over the range of concentration of comb-branch additives investigated. We attribute this discrepancy in rheological properties between simulation and experiment for PEO-modified colloidal suspensions to heterogeneous adsorption of the comb-branch polymers.

Role of Computational Simulations in Heart Valve Dynamics and Design of Valvular Prostheses

Computational simulations are playing an increasingly important role in enhancing our understanding of the normal human physiological function, etiology of diseased states, surgical and interventional planning, and in the design and evaluation of artificial implants. Researchers are taking advantage of computational simulations to speed up the initial design of implantable devices before a prototype is developed and hence able to reduce animal experimentation for the functional evaluation of the devices under development. A review of the reported studies to date relevant to the simulation of the native and prosthetic heart valve dynamics is the subject of the present paper. Potential future directions toward multi-scale simulation studies for our further understanding of the physiology and pathophysiology of heart valve dynamics and valvular implants are also discussed.

Intermediate filament-deficient cells are mechanically softer at large deformation: A multi-scale simulation study

The cell’s cytoskeleton, providing cells with structure and shape, consists of different structural proteins, including microtubules, actin microfilaments and intermediate filaments. It has been suggested that intermediate filaments play a crucial role in providing mechanical stability to cells. By utilizing a simple coarse-grained computational model of the intermediate filament network in eukaryotic cells, we show here that intermediate filaments play a significant role in the cell mechanical behavior at large deformation, and reveal mechanistic insight into cell deformation under varying intermediate filament densities. We find that intermediate filament-deficient cells display an altered mechanical behavior, featuring a softer mechanical response at large deformation while the mechanical properties remain largely unchanged under small deformation. We compare the results with experimental studies in vimentin-deficient cells, showing good qualitative agreement. Our results suggest that intermediate filaments contribute to cell stiffness and deformation at large deformation, and thus play a significant role in maintaining cell structural integrity in response to applied stress and strain, in agreement with earlier hypotheses. The simulation results also suggest that changes in the filament density result in profound alterations of the deformation state of the cell nucleus, leading to greater stretch in the direction of loading and greater contraction in the orthogonal direction as the intermediate filament density is increased. Our model opens the door to future studies to investigate disease states, the effects of amino acid mutations and how structural changes at different levels in the cell’s structural makeup influence biomechanical properties.