Molecular Dynamics Simulation Technique Research Articles

Nickel nanoparticles inside carbon nanostructures: atomistic simulation

Ni nanoparticle on a graphene substrate, inside the fullerene and carbon nanotube was studied by molecular dynamics simulation technique. Morse interatomic potential have been used for Ni-Ni and Ni-C interactions, and AIREBO potential has been used for C-C interaction. The pairwise Morse potential was chosen for the description of the Ni–C interaction because of its simplicity. It is shown that Morse potential can satisfactory reproduce the properties of graphene-nickel system. The effect of boundary conditions on the interaction of Ni nanoparticle and graphene sheet are investigated. It is shown, that if the edges of graphene plane are set to be free, coverage of Ni nanoparticle by graphene or just crumpling of graphene is observed depending on the size of nanoparticle. It is found, that Ni nanoparticle tend to attach to the carbon surface - graphene plane or the shell of fullerene and nanotube. Moreover, Ni nanoparticle induce the deformation of the surface of carbon polymorph. The obtained results are potentially important for understanding of the fabrication of metal-carbon composites and interaction between graphene and metal nanoparticles in such a system.

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor.

Karrikins (KARs) are a class of smoke-derived seed germination stimulants with great significance in both agriculture and plant biology. By means of direct binding to the receptor protein KAI2, the compounds can initiate the KAR signal transduction pathway, hence triggering germination of the dormant seeds in the soil. In the research, several molecular dynamics (MD) simulation techniques were properly integrated to investigate the binding process of KAR1 to KAI2 and reveal the details of the whole binding event. The calculated binding free energy, -7.00 kcal/mol, is in good agreement with the experimental measurement, -6.83 kcal/mol. The obtained PMF profile indicates the existence of three intermediate states in the binding process. The analysis of the simulation trajectories demonstrates that, in the intermediate structures, KAR1 is stabilized by some hydrophobic residues (Phe26, Phe134, Leu142, Trp153, Phe157, Leu160, Phe194), along with several bridging water molecules, and meanwhile, the significant shifting occurs in the local conformation of the protein as the ligand's binding. A series of the residues (Gln141-Phe157) on the so-called "cap domain" are proposed to be responsible for capturing the ligand at the initial stage of the binding. Besides, the changes of the ligand's poses are also quantitatively characterized by the proper choice of the coordinate system. Our work will contribute to the more penetrating understanding of the ligand binding process and the receptor affinity difference between several members in the KAR family and help design new, more effective germination stimulants.

Antifungal and physicochemical properties of inclusion complexes based on β-cyclodextrin and essential oil derivatives.

Inclusion complexes based on β-cyclodextrin (β-CD) and antimicrobial compounds, were prepared by co-precipitation method, and characterized by entrapment efficiency (EE), thermal analysis, X-ray diffraction, 1H NMR spectroscopy, and water sorption. In addition, experiments associated to evaluate the effect of relative humidity on the release of active compounds and antifungal tests were performed. The analysis evidenced the encapsulation of active compounds into the β-CD structure with EE of 91 ± 4.1% and 66 ± 2.1% for β-CD/cinnamaldehyde and β-CD/eugenol complexes, respectively. Additionally, high relative humidities favored the release of active compounds from inclusion complexes. On the other hand, inclusion complexes were able to control the growth of B. cinerea, which was evidenced by a reduction of its mycelialradial growth. Finally, specific interactions between the active compounds and β-CD were evaluated through molecular dynamics simulation techniques. According to the obtained results, these complexes could be applied as additives in the design of antifungal packaging.

Dynamics in Acetamide+LiNO3 Deep Eutectic Solvents

Deep eutectic solvents (DES) are composite mixtures which have freezing point lesser than that of their individual components. A mixture of acetamide and lithium nitrate in the molar ratio of 78:22 is observed to form a DES with freezing point below room temperature. Here we report nanoscale dynamics in acetamide + LiNO3 DES as studied using quasielastic neutron scattering (QENS) and molecular dynamics (MD) simulation techniques. The results of MD simulation show a transient subdiffusive motion for acetamide molecules. The acetamide molecules form a hydrogen-bond network with its neighbouring set of molecules resulting in a transient cage. The motion of the acetamide molecules is described by considering a power law memory kernel for the relaxation of the cage. The intermediate scattering function obtained from the QENS experiments of DES are described using stretched exponential relaxation function. The power law exponent describing the results of MD simulation is found to match well with the stretching exponent obtained from QENS experiments.

Simulation of graphene–fullerene nanohybrid structure

In the present simulation study, the structure and dynamics of graphene–fullerene nanocomposite has been investigated using all atom molecular dynamics simulation technique. The formation of graphene–fullerene nanocomposite constituting graphene and self-assembly of 12 bucky balls has been demonstrated. The structure, size, interparticle separation, spatial distribution, temperature effect, mobility and conformation of graphene–fullerene nanocomposite, and the influence of single and two layers of graphene on the structure of graphene–fullerene nanocomposite have been determined and discussed in detail. This simulation result may possibly aid the design and development of graphene–fullerene hybrid nanomaterials for future biological and technological applications.

Stimuli-Responsive Room-Temperature N-Heteroacene Liquid: In Situ Observation of the Self-Assembling Process and Its Multiple Properties.

A novel stimuli-responsive room-temperature photoluminescent liquid 1 based on the N-heteroacene framework is developed and analyzed by several experiments such as differential scanning calorimetry, X-ray diffraction, dynamic viscoelasticity measurement, in situ observation by optical and polarized optical microscopes, UV-vis absorption and fluorescence spectroscopy, and by theoretical methods such as ab initio calculation and molecular dynamics (MD) computer simulation techniques. In contrast to stimuli-responsive solid materials reported previously, liquid 1 in response to HCl vapor as a single stimulus can involve dramatically multiple changes in physical properties such as rheological behavior, morphology, as well as photoluminescence. The present ab initio calculation and microsecond-timescale MD simulations reveal that the complexation of 1 and HCl molecules induces a large dipole moment, leading to the formation of stacking structures because of their dipole-dipole interaction. Upon exposure to HCl vapor, in situ microscopic observation of the stimuli-responsive liquid elucidates a self-assembling process involving the formation of the wrinkle structure in a micrometer scale, indicating disorder-order phase transition. Further exposure of 1 to HCl vapor from seconds to hours has an influence on the macroscopic physical properties such as viscosity, viscoelasticity, and photoluminescent colors. The synergy between the experimental and theoretical investigations opens a new strategy to develop a novel class of stimuli-responsive materials showing multiple changes in physical properties.

Membrane partitioning of peptide aggregates: coarse-grained molecular dynamics simulations

Coarse-grained molecular dynamics (CGMD) simulation technique (MARTINI force field) is applied to monitor the aggregation of helical peptides representing the transmembrane sequence and its extension of bone marrow stromal cell antigen 2 (BST-2). One of the peptides is coupled with a protein transducing domain (PTD) of nine arginine residues (R9) at its N-terminal side as well as a peptide, pep11**, which has been shown to bind to human papilloma virus 16 (HPV16) E6 oncoprotein. A short hydrophobic stretch of the transmembrane domain (TMD) of BST-2 aggregates the fastest and inserts into a lipid membrane. An aggregate of R9-pep11** attaches to the membrane via simultaneous contact of many arginine residues. Monomers from the aggregates of the shortest of the hydrophobic TMDs dissolve into the opposing leaflet when the aggregate spans the bilayer. A ‘flipping’ of the individual monomeric peptides is not observed.Communicated by Ramaswamy H. Sarma

Evaluation of maltose binding to proteinase K: Insights from spectroscopic and computational approach

The change in structure, function of proteinase K in the presence of maltose was studied using spectroscopic and computational techniques. UV–Vis spectroscopy results reveal with the addition of maltose, the peaks of proteinase K didn't show any shifts. The intrinsic fluorescence intensity was decreased regularly with rising the ligand concentration. These results suggest that the quenching mode is dynamic quenching. Far-UV circular dichroism (CD) studies showed a low decrease in the β-sheet, β-turn and the large increase in the α-helix. The activity of proteinase K was increased in the presence of maltose. Thus, maltose is an activator for proteinase K. Molecular docking results show a negative value for the Gibbs free energy. On the other hand, the thermal stability of proteinase K was investigated in the presence of maltose over the temperature range (298–353) K. Obtained data indicate the thermal stability of proteinase K will be reduced when the concentration of maltose increase. These results are confirmed by the molecular dynamic simulation technique.

In Search of a Structural Pattern in Crazy Sugarsidentification of Conformation Clusters of the Oligosaccharides Within Glycoproteins with LEUS

Oligosaccharides within glycoproteins, also called glycans, have been recognized to have critical biological roles: in regulation of the immune system, cellular growth, cell-cell adhesion, infection, inflammation and malignant transformations. Their structural diversity has enabled them to have this broad range of functionalities. Glycans can be built from monomers that differ in size, linkage types, linkage positions and charges. Furthermore, there is a lack of reliable 3D structural information from experimental techniques because of their flexible nature. To tackle this problem, we used enhanced molecular dynamics simulation techniques to offer 3D models in the absence of experimental structural data. With this aim, ‘motion libraries’ of all disaccharides constituting the most common glycans were constructed using an enhanced sampling method, local elevation umbrella sampling (LEUS). In the build-up phase, biased potentials were constructed for the glycosidic linkages of disaccharides, which were subsequently used to sample the conformational space for larger oligosaccharides. First, the effect of consecutive linkages on the disaccharide free-energy landscape was assessed at the trisaccharide level. Next, some of the most common human glycans, such as complex and high-mannose N-glycans, were modelled. In addition to these glycans, the effect of core-fucosylation is investigated on these models. The disaccharide motion libraries are used to sample the conformation space of these oligosaccharide units along the glycosidic dihedral angle. Several clustering schemes are used to identify different structural patterns observed in the different glycan types. Here, we show preliminary results for solution structure clusters of the most common glycans found in human glycoproteins.

Detection and Mapping of dsDNA Breaks using Graphene Nanopore Transistor

Single-strand DNA (ssDNA) breaks that are often converted into DNA double-strand (dsDNA) breaks make up a vast majority of lesions a normal human cell undergoes everyday. If the repair mechanism fails, the dsDNA break can cause chromosomal instability leading to tumorigenesis. Additionally, a single break in a critical gene can cause the cell to undergo apoptosis. Existing genome sequencing techniques are not suitable for detecting such changes directly. As an alternative methodology, we propose to employ graphene-Quantum Point Contact nanopore transistor to detect and map defects in the DNA backbone, as miniscule as ssDNA breaks, efficiently using electronic sheet currents obtained across the transistor membrane. For this purpose, we use large-scale comprehensive all-atom molecular dynamics simulation techniques accompanied with electronic transport calculations, data denoising and signal detection. In all our simulations, we observe the molecule sticking in the pore at the nicked site due to strong hydrophobic attraction between the graphene membrane and the damaged-backbone. While the ionic currents calculated for the translocation of 20 base-pair dsDNA strand with a break in the backbone does not show any distinct signature from the nicked-site in the signal, a clear dip is seen in the transverse sheet current signal corresponding to the location of the breakage, thereby enabling us to detect and map these damages, electronically. We validated our methodology by detecting other sequence specific dsDNA breaks along randomly sequenced strands. We strongly believe such a detection mechanism enables the development of versatile semiconductor electronics for early cancer detection caused by structural modification of the genome.

Computational insights into the role of \u03b1-strand/sheet in aggregation of \u03b1-synuclein

The α-synuclein is a major component of amyloid fibrils found in Lewy bodies, the characteristic intracellular proteinaceous deposits which are pathological hallmarks of neurodegenerative diseases such as Parkinson’s disease (PD) and dementia. It is an intrinsically disordered protein that may undergo dramatic structural changes to form amyloid fibrils. Aggregation process from α-synuclein monomers to amyloid fibrils through oligomeric intermediates is considered as the disease-causative toxic mechanism. However, mechanism underlying aggregation is not well-known despite several attempts. To characterize the mechanism, we have explored the effects of pH and temperature on the structural properties of wild-type and mutant α-synuclein using molecular dynamics (MD) simulation technique. MD studies suggested that amyloid fibrils can grow by monomer. Conformational transformation of the natively unfolded protein into partially folded intermediate could be accountable for aggregation and fibrillation. An intermediate α-strand was observed in the hydrophobic non-amyloid-β component (NAC) region of α-synuclein that could proceed to α-sheet and initiate early assembly events. Water network around the intermediate was analyzed to determine its influence on the α-strand structure. Findings of this study provide novel insights into possible mechanism of α-synuclein aggregation and promising neuroprotective strategy that could aid alleviate PD and its symptoms.

Biomolecular interactions of lysosomotropic surfactants with cytochrome c and its effect on the protein conformation: A biophysical approach

The molecular interactions between two single-chain lysosomotropic surfactants DMM-11 (2-Dodecanoyloxyethyl)trimethylammonium bromide) and DMPM-11 (2-Dodecanoyloxypropyl)trimethylammonium bromide) with a small heme-protein (cytochrome c (cyt-c)) in Hepes buffer (pH = 7.4) were extensively investigated by surface tension, dynamic light scattering (DLS), circular dichroism (CD) and fluorescence spectroscopy in combination with molecular dynamic simulation techniques. The results demonstrated that surfactants can destroy the hydrophobic cavity of cyt-c, make the α-helical become loose and convert it into the β-sheet structure. The interactions between surfactants and cyt-c are mainly hydrophobic. Molecular modelling approaches were also used to gather a deeper insight on the binding of lysosomotropic surfactants with cyt-c and the in silico results were found to be in good agreement with the experimental ones. This study provides a molecular basis for the applications of protein-surfactant complexes in biological, food, pharmaceutical, industrial and cosmetic systems.

Identification of enzyme(s) capable of degrading endosulfan and endosulfan sulfate using in silico techniques

Endosulfan is one of the most widely used organochlorine cyclodiene insecticides. Microbial oxidation of endosulfan forms endosulfan sulfate, which is more or less toxic and persistent as endosulfan. Due to lack of specificity and efficiency of microbial bioremediation technique in the field conditions, enzymatic bioremediation is receiving huge attention to clean-up the environment. In the present study, X-ray crystal structures of enzymes from Brookhaven Protein Data Bank were screened for their potential to degrade endosulfan and endosulfan sulfate using molecular docking and molecular dynamics simulation techniques. A phenol hydroxylase, 1PN0 from Trichosporon cutaneum was found to have the potential to degrade both α-endosulfan and endosulfan sulfate while a bacterial CotA laccase, 3ZDW from Bacillus subtilis has the potential to degrade α-endosulfan. The in silico result correlate with in vitro degradation study using two different strains of Trichosporon cutaneum. In vitro degradation study found that the fungal strain was capable of degrading 60.36% α-endosulfan, 70.73% β-endosulfan, and 52.08% endosulfan sulfate. The presence of phenol hydroxylase inhibitor in the sulfur-free medium with endosulfan and endosulfan sulfate as sole sulfur source inhibits the growth of both the fungal strains. Such in silico techniques can provide an easy and reliable way to speed up the development of bioremediation processes through rapid identification of potential enzymes and microbes to counter the ever-increasing number of toxic compounds in the environment.

A computational study on thermo-mechanical characterization of carbon nanotube reinforced natural rubber

ABSTRACTA computational study based on molecular dynamics simulation technique has been used to predict the mechanical and thermal behavior of carbon nanotube (CNT) reinforced natural rubber (NR) composites. A single-walled 5,5 armchair type CNT has been used for this purpose. In this study, a comparison has been made between pristine and functionalized CNTs. The functionalization groups used in this study were carboxylic (COOH), ester (COOCH3) and hydroxyl (OH). The studies show the improvement in elastic properties of developed composites in the presence of functionalization group. In addition, the effect of volume fraction and 1-25% addition of functionalization group has been studied. The obtained simulation results show the better load-transfer capacity in developed polymer system and improved elastic modulus. Thermal properties of developed composite systems were studied by non-equilibrium molecular dynamics method (NEMD). The addition of functionalized CNTs shows enhanced mechanical and thermal properties.

Interactive Visualization Technique of Molecular Dynamics Simulation by Using HMD and VR

Interactive Visualization Technique of Molecular Dynamics Simulation by Using HMD and VR

Multidimensional insights involving electrochemical and in silico investigation into the corrosion inhibition of newly synthesized pyrazolotriazole derivatives on carbon steel in a HCl solution.

Herein, the anti-corrosion of carbon steel in 1 M HCl by two newly synthesized pyrazolotriazole derivatives, namely, 6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbonitrile (CPT) and 1-acetyl-6-methyl-1H-pyrazolo[5,1-c][1,2,4]triazole-7-carbothioamide (MPT), was studied using electrochemical, density functional theory (DFT), and molecular dynamics (MD) simulation techniques. The experimental results showed that the concentrations of inhibitors had a significant influence on their inhibition efficiencies. Potentiodynamic polarization curves indicated that the two pyrazolotriazoles were mixed-type inhibitors. DFT calculations were employed to explore the molecular activity, and MD simulations were performed to obtain the interaction energy between the inhibitor molecules and the iron surface. The findings obtained using the theoretical calculation techniques were consistent with those obtained via experiments.

Are Gaming-Enabled Graphic Processing Unit Cards Convenient for Molecular Dynamics Simulation?

In several fields of research, molecular dynamics simulation techniques are exploited to evaluate the temporal motion of particles constituting water, ions, small molecules, macromolecules, or more complex systems over time. These techniques are considered difficult to setup, computationally demanding and require high specialization and scientific skills. Moreover, they need specialized computing infrastructures to run faster and make the simulation of big systems feasible. Here, we have simulated 3 systems of increasing sizes on scientific- and gaming-enabled graphic processing unit (GPU) cards with Amber, GROMACS, and NAMD and measured their performance accounting also for the market prices of the GPU cards where they were run on.

Molecular modelling studies of quinazolinone derivatives as MMP-13 inhibitors by QSAR, molecular docking and molecular dynamics simulations techniques.

Matrix metalloproteinase-13 (MMP-13) is an attractive drug target for the treatment of osteoarthritis (OA). In this study, a series of quinazolinone derivatives as MMP-13 inhibitors were firstly systematically studied using QSAR, molecular docking and molecular dynamics (MD) simulation. The reliable CoMFA (q 2 = 0.646, r 2 = 0.992, R pred 2 = 0.829) and CoMSIA (q 2 = 0.704, r 2 = 0.992, R pred 2 = 0.839) models were constructed and verified by the Topomer CoMFA model. Results of contour maps indicated that the electrostatic, hydrophobic and H-bond acceptor fields primarily influenced the activity of MMP-13 inhibitors in the models. Several key residues (Ala238, Thr245, Thr247, Met253, Asn215 and Lys140) were identified as important factors to improve the activity and stability of the inhibitor through hydrogen bonding and electrostatic interaction. Based on these results, eight novel quinazolinones (D1-D8) were further designed. Additionally, all designed compounds showed good pharmacokinetic properties by ADMET predictions. Compounds D3 and D8 exhibited excellent predictive activity, and the 10 ns MD simulations analysis revealed that the hydrogen bonding interaction with residues (Ser250 and Gly248) was enhanced, and the small group in R2 and U-shaped conformation was of pivotal importance. These results provided strong guidance for the discovery and design of novel potential MMP-13 inhibitors.

Thermodynamic Study of Binary Systems Containing Carbon Dioxide and Associated Gases Using Molecular Simulation Techniques

The reduction of greenhouse gas (GHG) emissions has become an utmost objective for many industrialized countries. Industrial activities involving the combustion of fossil resources are responsible for a large part of the human induced carbon dioxide (CO2) emissions. The carbon dioxide capture and storage (CCS) has been already proven technically feasible and more recently the carbon dioxide capture and utilization (CCU) economically viable, to regulate CO2 emissions to the atmosphere. Depending on its origin and despite performed treatments, the injected CO2 may contain small amounts of associated gaseous components such as O2, N2, SOx, NOx, as well as traces of noble gases. The experimental knowledge of the thermodynamic behavior for such gas mixtures or even for some binary gas mixtures is often scarce. Molecular simulation techniques have been proven as cost-efficient alternatives to experimental measurements, especially when hazardous compounds and/or extreme pressure or temperature conditions are considered. These last years, we have devoted much effort to the use of molecular simulation techniques as well as to the development of accurate atomistic representations for gas molecules, to predict equilibrium and transport properties (phase envelopes, densities, viscosities, critical coordinates…) for mixtures containing CO2 and associated gaseous components, for conditions encountered in CCS and CCU stages. In this communication, we propose a compendium of data we previously obtained using Monte Carlo (MC) and Molecular Dynamics (MD) simulation techniques. Indeed, we have shown that molecular simulation tools used together with accurate force fields are efficient to predict equilibrium and transport properties for mixtures containing CO2 and associated gaseous components, and allow extrapolations to severe pressure or temperature conditions. This work illustrates how molecular simulations may be used as a tool to mitigate the lack of experimental data.

Atomistic simulation of strength properties of conventional and nano-structured materials

State-of-the-art supercomputing technologies allow addressing the problem of materials design and their properties change due to processing, storage and exploitation to direct large-scale Molecular Dynamics (MD) simulations. In the first part of the paper, by the example of fission materials we demonstrate the chain of MD simulation techniques developed to evaluate material properties change due to self-irradiation (so-called ageing). Starting from detailed microscopic Monte Carlo + MD calculations of damage cascade development and annealing resulting in a system of Primary Radiation Defects (PRD), the problems of PRD and radiogenic products accumulation and clustering are resolved by the application of Thermodynamic Integration Method. Finally, virtual samples of a material containing defects of determined morphology corresponding to a given age are subjected to a ‘mechanical loading’ to evaluate the effect of self-irradiation on mechanical strength properties. In the second part we consider issues of MD simulations of nano-structured materials, including effects of samples processing history (dislocation density) on mechanical properties, solidification and thermal recrystallization, as well as resistance to radiation loading. In conclusion the prospects of application of the techniques to structural materials which are, as a rule, multi-component aggregates are discussed with a number of straightforward examples.