Experimental Molecular Dynamics Research Articles

ПОШУК САЙТУ ЗВ'ЯЗУВАННЯ КАЛІКС [4] АРЕНІВ ІЗ КІНАЗОЮ ЛЕГКИХ ЛАНЦЮГІВ МІОЗИНУ МЕТОДОМ МОЛЕКУЛЯРНОЇ ДИНАМІКИ

Disruptions of the functional activity of human smooth muscle are associated with a significant number of pathological conditions of the human body. The myosin light-chain kinase is the key enzyme of the signaling cascade of neurohumoral signals in smooth muscle cells. Especially it is important in the long-term tonic contraction. Disruption of its kinase activity can lead to a weakening of the intercellular interaction of the epithelial and endothelial cells, disruption of functioning of the intestinal smooth muscles and vessels, complication of labor activity. At the moment the search for effectors of this enzyme is being carried out. The problem is that most drugs are removed at the general body level due to toxic effects on other tissues (organs) or adverse chemical and physical properties. Such substances require adapters (carriers) devoid of these defects and inert in vivo. The most promising are calixarenes. In this study, the molecular dynamics method was used to determine the stability of the calix [4] arenetetrazulphate complex and the myosin light-chain kinase catalytic domain. Initially, by means of docking, the most favorable position of calixaren was determined; it turned out to be a catalytic kinase pocket. After that, the molecular-dynamic experiment was conducted to determine the energy of interaction. It turned out that the total energy of the interaction is about -300 cJ/mol. This indicates the high stability of the complex. Due the location of the ligand, its effect on the enzymatic activity of the kinase can be assumed, therefore, the use of this calixarene as a drug delivery system seems inappropriate.

The molecular mechanism of robust macrophage immune responses induced by PEGylated molybdenum disulfide.

Molybdenum disulfide (MoS2), a representative hexagonal transition metal dichalcogenide (TMD), has been extensively exploited in biomedical applications due to its unique physicochemical properties and biocompatibility. However, the lack of adequate data regarding how MoS2 activates immunological responses of macrophages remains a key concern for its risk assessment. Here, we employ a combined theoretical and experimental approach to investigate the interactions of MoS2 and PEGylated MoS2 (MoS2-PEG) with macrophages. We first perform molecular dynamics simulations to examine the atomic-detailed interactions of MoS2 and MoS2-PEG nanoflakes with a realistic model of the macrophage membrane. We show that a small MoS2 nanoflake (edge length of 2.86 nm) is capable of penetrating the macrophage membrane independent of its concentration. We also demonstrate that when initiated with a corner point-on configuration, the surface-bound PEG chains of MoS2-PEG hinder its membrane insertion process, leading to a prolonged passage through the membrane. Moreover, when placed in a face-on arrangement initially, the MoS2-PEG exhibits a lower binding free energy than pristine MoS2 after its adsorption on the membrane surface. The PEG chains can even insert and get buried in the outer leaflet of the membrane, providing additional contact for membrane adsorption. Our flow cytometric experiments then show that the responses of macrophages to either MoS2-PEG or MoS2 are significantly higher than that of the control (no nanomaterial stimulus), with MoS2-PEG eliciting stronger cytokine secretion than the pristine MoS2. The characteristics of slower/prolonged membrane penetration and stronger membrane adsorption of MoS2-PEG compared to pristine MoS2 explain why it triggers more sustained stimulation and higher cytokine secretion in macrophages as observed in our experiments. Our findings reveal the underlying molecular mechanism of how MoS2-PEG influences the immune responses and suggest its potential applications in nanomedicine involving immune stimulation.

Amphiphile-Induced Phase Transition of Liquid Crystals at Aqueous Interfaces.

Monolayer assemblies of amphiphiles at planar interfaces between thermotropic liquid crystals (LCs) and an aqueous phase can give rise to configurational transitions of the underlying LCs. A common assumption has been that a reconfiguration of the LC phase is caused by an interdigitation of the hydrophobic tails of amphiphiles with the molecules of the LC at the interface. A different mechanism is discovered here, whereby reorientation of the LC systems is shown to occur through lowering of the orientation-dependent surface energy of the LC due to formation of a thin isotropic layer at the aqueous interface. Using a combination of atomistic molecular dynamics simulations and experiments, we demonstrate that a monolayer of specific amphiphiles at an aqueous interface can cause a local nematic-to-isotropic phase transition of the LC by disturbing the antiparallel configuration of the LC molecules. These results provide new insights into the interfacial, molecular-level organization of LCs that can be exploited for rational design of biological sensors and responsive systems.

Interaction between low molecular weight carboxylic acids and muscovite: Molecular dynamic simulation and experiment study

Interface phenomena between low molecular weight (LMW) carboxylic acids and muscovite was investigated through molecular dynamic simulation and experiment, where the typical monocarboxylic acids including formic acid (C1), acetic acid (C2), propionic acid (C3) and butyric acid (C4) were used as models. Density distribution, adsorption energy, root mean square dynamic (RMSD) of carboxylic acids on water-muscovite interface were calculated through molecular dynamic simulation, and the advanced characterization methods, such as ATR-FTIR spectra, AFM images and contact angle were performed to test and verify the relative simulation findings. The molecular simulation showed that carboxylic acids adsorbed on surface of muscovite through hydrogen bond between H atom of COOH functional group of carboxylic acid and O atom of muscovite, belong to outer sphere adsorption, and ATR-FTIR spectra and AFM images confirmed this finding. Adsorption energy for long carbon chain carboxylic acid (C4) was higher than that for short carbon chain carboxylic acid (C1, C2 and C3) due to the effect of carboxylic acid diffusion on water-muscovite interface. The hydrophilic functional group COOH of carboxylic acids preferably adsorbed on muscovite surface, while the hydrophobic functional groups CH3 and CH2 of carboxylic acids were far from the muscovite surface. So, the hydrophobicity on muscovite surface increased due to the adsorption of carboxylic acids, which resulted in the increase of contact angle of water on muscovite surface.

The Kinetics of the Liquid Phase Nucleation in a Stretched FCC Crystal: A Molecular Dynamics Simulation

The kinetics of a spontaneous formation of liquid phase in a stretched (superheated) Lennard-Jones fcc crystal is studied. Molecular dynamics experiments are used to determine the main parameters of the nucleation process: nucleation frequency J, diffusion coefficient of nuclei D*, nonequilibrium Zel’dovich factor Z, and critical nucleus size R*. The calculations are performed at negative pressures from the endpoint of the melting line and at positive pressures that are higher by a factor of eight than the critical pressure. The simulation results are compared to the classical homogeneous nucleation theory. It is found that the theory qualitatively correctly reproduces the dynamics of developing the process. The theory and the simulation demonstrate good quantitative agreement for the transition rate of the liquid phase nucleus through the critical size, but there is large difference in the numbers of critical nuclei in the unit volume of the metastable phase. In the case of significant superheatings and negative pressures, the contribution of the energy of elastic stresses to the moving force of the phase transformation is small and it can be neglected in a first approximation. The mismatch between the theory and the simulation results can be eliminated taking that the surface free energy of a curved “crystal–liquid droplet” interface is smaller than that of a plane interface by 30–35%.

Study on the solid thermal insulation mechanisms of nitrogen-doped graphene aerogels by molecular dynamics simulations and experiments

Reduced graphene oxide aerogels (rGO aerogels) may become the next generation of thermal insulation materials. In this paper, the solid thermal insulation mechanisms of nitrogen-doped graphene aerogels (NDGA, rGO aerogels) were studied using nonequilibrium molecular dynamics simulations and experiments. The solid thermal resistance of NDGA is composed of the thermal resistance in graphene and the interfacial thermal resistance. Since the grain size of graphene in NDGA is much smaller than the phonon mean free path and the graphene sheet size, the defects and grafting play much more significant roles in lowering the thermal conductivity of graphene compared to sheet size. Vacancy defects show higher efficiency in lowering the thermal conductivity. Co-grafting and pyrrolic N addition further decrease the thermal conductivity. The interfacial thermal resistance of overlapped graphene is significant. It decreases with the increase of connection number. Bridging prevents the overlap of graphene, suppressing the heat transfer through overlap position. The thermal resistance in graphene plays a more significant role in the solid thermal insulation of NDGA compared to the interfacial thermal resistance. Overall, these findings provide a more thorough understanding of the solid thermal insulation mechanisms of NDGA. They are significant for the optimization and application of the aerogels.

Understanding the Intrinsic Carrier Transport in Highly Oriented Poly(3-hexylthiophene): Effect of Side Chain Regioregularity.

The fundamental understanding of the influence of molecular structure on the carrier transport properties in the field of organic thermoelectrics (OTEs) is a big challenge since the carrier transport behavior in conducting polymers reveals average properties contributed from all carrier transport channels, including those through intra-chain, inter-chain, inter-grain, and hopping between disordered localized sites. Here, combining molecular dynamics simulations and experiments, we investigated the carrier transport properties of doped highly oriented poly(3-hexylthiophene) (P3HT) films with different side-chain regioregularity. It is demonstrated that the substitution of side chains can not only take effect on the carrier transport edge, but also on the dimensionality of the transport paths and as a result, on the carrier mobility. Conductive atomic force microscopy (C-AFM) study as well as temperature-dependent measurements of the electrical conductivity clearly showed ordered local current paths in the regular side chain P3HT films, while random paths prevailed in the irregular sample. Regular side chain substitution can be activated more easily and favors one-dimensional transport along the backbone chain direction, while the irregular sample presents the three-dimensional electron hopping behavior. As a consequence, the regular side chain P3HT samples demonstrated high carrier mobility of 2.9 ± 0.3 cm2/V·s, which is more than one order of magnitude higher than that in irregular side chain P3HT films, resulting in a maximum thermoelectric (TE) power factor of 39.1 ± 2.5 μW/mK2 at room temperature. These findings would formulate design rules for organic semiconductors based on these complex systems, and especially assist in the design of high performance OTE polymers.

Lifting ordered surfaces: Ellipsoidal nematic shells.

When a material surface is functionalized so as to acquire some type of order, functionalization of which soft condensed matter systems have recently provided many interesting examples, the modeler faces an alternative. Either the order is described on the curved, physical surface where it belongs, or it is described on a flat surface that is unrolled as preimage of the physical surface under a suitable height function. This paper applies a general method that pursues the latter avenue by lifting whatever order tensor is deemed appropriate from a flat to a curved surface. We specialize this method to nematic shells, for which it also provides a simple but perhaps convincing interpretation of the outcomes of some molecular dynamics experiments on ellipsoidal shells.

Significance of catalase-peroxidase (KatG) mutations in mediating isoniazid resistance in clinical strains of Mycobacterium tuberculosis.

Isoniazid (INH) is still the most important first-line antitubercular drug. INH resistance is regarded as a major impediment to the tuberculosis (TB) control programme and contributes to the emergence of multidrug-resistant strains. Mutation at position 315 in the katG gene, encoding the catalase-peroxidase (KatG) enzyme, is the major cause of INH resistance in Mycobacterium tuberculosis. Therefore, investigation of the molecular mechanisms of INH resistance is the need of the hour. To understand the clinical importance of KatG mutants (MTs) leading to INH resistance, in this study five MTs (S315T, S315I, S315R, S315N and S315G) were modelled, docked and interacted with INH in dynamic state. The binding affinity based on docking was found to be higher for MTs than for wild-type (WT) isolates, except for MT-S315R, indicating rigid binding of INH with MT proteins compared with the flexible binding seen in the WT. Analysis of molecular dynamics (MD) experiments suggested that fluctuations and deviations were higher at the INH binding residues for MTs than for the WT. Reduction in the hydrogen bond network after MD in all KatG enzymes implies an increase in the flexibility and stability of protein structures. Superimposition of MTs upon the WT structure showed a significant deviation that varies for the different MTs. It can be inferred that the five KatG MTs affect enzyme activity in different ways, which could be attributed to conformational changes in MT KatG that result in altered binding affinity to INH and eventually to INH resistance.

Enhancing the Matrix Addressing of Flexible Sensory Arrays by a Highly Nonlinear Threshold Switch.

The increasing need for smart systems in healthcare, wearable, and soft robotics is creating demand for low-power sensory circuits that can detect pressure, temperature, strain, and other local variables. Among the most critical requirements, the matrix circuitry to address the individual sensor device must be sensitive, immune to disturbances, and flexible within a high-density sensory array. Here, a strategy is reported to enhance the matrix addressing of a fully integrated flexible sensory array with an improvement of 108 fold in the maximum readout value of impedance by a bidirectional threshold switch. The threshold switch shows high flexibility (bendable to a radius of about 1 mm) and a high nonlinearity of ≈1010 by using a nanocontact structure strategy, which is revealed and validated by molecular dynamics simulations and experiments at variable mechanical stress. Such a flexible electronic switch enables a new generation of large-scale flexible and stretchable electronic and optoelectronic systems.

The prediction of upper limit of copper content in CoBCu glass-forming alloys

The soft magnetic properties of ferromagnetic nanocrystalline alloys can be enhanced considerably by addition of copper until the upper limit of Cu content which is unknown at present. This study explored the upper limit of Cu content in the Co81−XB19CuX (X = 2, 3 and 5) alloy system using ab initio molecular dynamics simulations and experiments. It was found that when the Cu content rose above 2 at%, the first-nearest-neighbor peaks of partial pair distribution function for Cu-Cu pair became stronger steadily with the decreasing temperature, demonstrating that Cu clusters were formed during the quenching processes from initial melt. As to the Cu content was less than or equal to 2 at%, the trace of such clusters was difficult to find. So the maximal Cu content in Co81−XB19CuX alloys in as-quenched amorphous state was predicted to be less than 2 at%. Co81−XB19CuX ribbons were prepared using the melt-spinning technique with as large cooling ability as possible. Structure analysis results from X-ray diffraction patterns of the three as-quenched alloys supported the above theoretical predictions. These results would provide a theoretical reference for the design of ferromagnetic nanocrystalline alloys.

Water and salt dynamics in multilayer graphene oxide (GO) membrane: Role of lateral sheet dimensions

Dependence of salt rejection efficiency and water permeability of layered graphene oxide (GO) membranes on the lateral dimension of constituting sheets are studied through equilibrium molecular dynamic (MD) simulation and experiments. This study suggests that with increasing sheets dimension permeability of the GO membranes decreases but its selectivity increases. The velocity and permeation time of the water molecules while permeating through the membrane are influenced to a greater extent by the pore offset distance (W) of the membranes. More over the larger pore offset distance increases the path length that the water molecules and ions have to traverse for permeating through the layered GO membranes. Based on the simple technique discussed in this work, one can construct GO membranes of required water permeability and salt rejection without the application of any foreign nanomaterials with the GO membrane, which retains the inherent selectivity of the GO membranes. This work also provides the effect of internal structure of GO membrane on the atomistic level details of the solvation shell of ions while they are permeating through the membrane.

Contact Angle Analysis for the Prediction of Defect States of Graphene Grafted with Functional Groups

AbstractMass production of graphene is being actively pursued for applications in electronics and energy devices. However, a rapid and simple method to identify the defect states of graphene (which significantly affects the electronic property), prior to the fabrication of the devices, needs to be developed. The manufacturing process requires an easy assessment tool to identify the characteristics of the defects while avoiding cumbersome measurements. This study demonstrates the contact angle analysis to be a plausible assessment tool with the help of molecular dynamics simulations and experiments. The simulations are performed for water droplets on graphene grafted with the most probable functional groups. The contact angle and the shape of the water droplets are interpreted to estimate the type and density of the defects in graphene. This technique can be used as a screening step to identify defective graphene.

Exploring the mechanistic insights of Cas scaffolding protein family member 4 with protein tyrosine kinase 2 in Alzheimer's disease by evaluating protein interactions through molecular docking and dynamic simulations.

Cas scaffolding protein family member 4 and protein tyrosine kinase 2 are signaling proteins, which are involved in neuritic plaques burden, neurofibrillary tangles, and disruption of synaptic connections in Alzheimer's disease. In the current study, a computational approach was employed to explore the active binding sites of Cas scaffolding protein family member 4 and protein tyrosine kinase 2 proteins and their significant role in the activation of downstream signaling pathways. Sequential and structural analyses were performed on Cas scaffolding protein family member 4 and protein tyrosine kinase 2 to identify their core active binding sites. Molecular docking servers were used to predict the common interacting residues in both Cas scaffolding protein family member 4 and protein tyrosine kinase 2 and their involvement in Alzheimer's disease-mediated pathways. Furthermore, the results from molecular dynamic simulation experiment show the stability of targeted proteins. In addition, the generated root mean square deviations and fluctuations, solvent-accessible surface area, and gyration graphs also depict their backbone stability and compactness, respectively. A better understanding of CAS and their interconnected protein signaling cascade may help provide a treatment for Alzheimer's disease. Further, Cas scaffolding protein family member 4 could be used as a novel target for the treatment of Alzheimer's disease by inhibiting the protein tyrosine kinase 2 pathway.

Necessary Duration of Molecular Dynamics Simulation for Calculation of Self-Diffusion Coefficient during Migration of Different Point Defects in Nickel

The evaluation of the necessary duration of molecular dynamics experiment for the calculation of the selfdiffusion coefficient during migration of different point defects in Ni (vacancy, bivacancy, self-interstitial atom, hydrogen atom) is conducted in this paper. The mentioned defects have different mobility that results in different intensities of atoms displacements caused by migration of the defect. The accuracy of diffusion coefficient calculation is related to the accuracy of estimation of rootmean-square changes of atoms coordinates. Consequently, the accuracy increases with the increase of moleculardynamic experiment duration t, the temperature T, and the mobility of the defect initiating the diffusion. To describe the interatomic interactions, the multi-particle Cleri-Rosato potential is used in the study. It is shown that the simulation duration of 100 ps is enough to calculate the diffusion coefficient when the temperature is higher than 0.6 of melting point. When calculating the diffusion coefficient of impurity in a metal crystal (for example, the hydrogen impurity), it is possible to decrease the root mean square error of displacement evaluation of impurity atoms by increasing the number of impurity atoms.DOI 10.14258/izvasu(2018)1-06

Ideal and Ultimate Tensile Strength of a Solid Body

The mechanical stability of an ideal elastic solid under infinitesimal and finitesimal changes in its state parameters is considered. The temperature and density dependences of the isothermic moduli of bulk compression K, simple shear, and tetragonal shear in a Lennard-Jones face-centered cubic (FCC) crystal have been determined by means of molecular dynamic experiments in the region of stable and metastable states. It has been shown that the crystalline phase remains stable under long-wave spatially nonuniform density fluctuations on the spinodal (K = 0) at pressures below the pressure of the endpoint of the melting line (p < pK < 0). Here, the critical nucleus formation work is also finitesimal. Hence, spinodal states in quasisteady- state processes at p < 0 not only are attainable, but the transition across the spinodal without destroying the homogeneity in the substance also proves to be feasible. In this case, the boundary of the ideal strength of a solid is set by the vanishing of the uniaxial compression modulus \(\tilde K\) for a certain specified deformation direction. The spinodal also is not the boundary of the ideal strength of a solid at positive and small negative pressures. A solid loses its ability for a restorative response to finitesimal spatially nonuniform density disturbances before the spinodal (\(\tilde K\) = 0) is attained.

Structure, thermal expansion coefficient and phase stability of La2(Zr0.7Ce0.3)2O7 studied by molecular dynamic simulation and experiment

This paper presents structure, thermal expansion coefficient and phase stability of La2(Zr0.7Ce0.3)2O7 (LZ7C3) ceramic by both theoretical and experimental results. It was found out that LZ7C3 powders had a pyrochlore structure after being heat-treated at temperatures higher than 1473 K or higher according to XRD and TEM results. The calculated average thermal expansion coefficient (TEC) was 7.12 × 10−6 K−1, which is a little smaller than experiment result, but changes of calculated average TECs of LZ, YSZ and LZ7C3 had the same trend with experimental results. Finally, the radial distribution function (RDF) was calculated to study the phase stability of LZ7C3.

Selectivity and Mechanism of Fengycin, an Antimicrobial Lipopeptide, from Molecular Dynamics.

Fengycin is a cyclic lipopeptide used as an agricultural fungicide. It is synthesized by Bacillus subtilis as an immune response against fungal infection and functions by damaging the target's cell membrane. Previous molecular dynamics simulations and experiments have led to the hypothesis that the aggregation of fengycins on the membrane surface plays a key role in cell disruption. Here, we used microsecond-scale all-atom molecular dynamics simulations to understand the specificity, selectivity, and structure of fengycin oligomers. Our simulations suggest that fengycin is more likely to form stable oligomers in model fungal membranes (phosphatidylcholine) compared to the model bacterial membranes (phosphatidylethanolamine:phosphatidylglycerol). Furthermore, we characterize the differences in the structure and kinetics of the membrane-bound aggregates and discuss their functional implications.

Molecular dynamics simulation and experiment research of cutting-tool wear mechanism for cutting aluminum alloy

In order to reveal the wear mechanism of diamond tool in precision cutting large-aperture aluminum alloy mirror, molecular dynamics simulation is carried out in this work. The simulation results indicate that diffusion wear is the dominant way of the tool wear, which is in consistent with the cutting experiment. EDS of the aluminum alloy chips shows that Cu elements result in the phenomenon of chemical wear for diamond tool in the precision cutting process. Therefore, the wear mechanism of diamond tool in precision cutting large-aperture aluminum alloy mirror is a combination of diffusion wear and chemical wear. In addition, through the micro topography of the diamond tool wear zone, it can be found that the flank wear is the dominant form of the cutting tool. The results of the orthogonal experiment show that the influence of the tool clearance and feed rate on tool wear is greater than that of the cutting speed and tool arc radius. The results of single-factor experiment indicate that with the increase of the feed rate, the tool wear increases. While with the increase of the tool clearance, the tool wear decreases.

In-silico prediction of sweetness using structure-activity relationship models

Quantitative structure activity relationship (QSAR) models appear to be an ideal tool for quick screening of promising candidates from a vast library of molecules, which can then be further designed, synthesized and tested using a combination of rigorous first principle simulations, such as molecular docking, molecular dynamics simulation and experiments. In this study, QSAR models have been built with an extensive dataset of 487 compounds to predict the sweetness potency relative to sucrose (ranging 0.2–220,000). The whole dataset was randomly split into training and test sets in a 70:30 ratio. The models were developed using Genetic Function Approximation (Rtest2 = 0.832) and Artificial Neural Network (Rtest2 = 0.831). Our models thus offer a convenient route for fast screening of molecules prior to synthesis and testing. Additionally, this study can supplement a molecular modelling approach to improve binding of molecules with sweet taste receptors, leading to design of novel sweeteners.