Experimental Molecular Dynamics Research Articles

Structural responses of kiwifruit allergen Act d 2 to thermal and electric field stresses based on molecular dynamics simulations and experiments.

Kiwifruit is considered to be the most common plant-based food causing allergic reactions, after peanuts, soybeans, and wheat. These responses are triggered by the proteins in kiwifruit. Modifying the structures of these allergenic proteins (epitopes) through external stresses may decrease their specific binding capacity with antibodies, resulting in a decrease in kiwifruit allergenicity. To provide a visual insight into the structural changes of Act d 2, we treated it with a thermal force and an oscillating electric field using molecular dynamics (MD) simulations. The results showed that Act d 2 is a heat-stable protein, while the electric field combined with thermal stress significantly affected its secondary structure and surface properties, which could result in conformational changes. The results obtained from ELISA tests showed that the combination of the thermal force and electric field significantly reduced the Ig-E binding capacity of Act d 2 by 75.3%, accompanied with obvious losses of alpha-helix and turn structures.

Outlooks for development of silicon nanoparticle memory cells

Phase change memory is based on changes in the optical, electrical or other properties of materials during phase transitions, e.g. an amorphous to crystalline transition. Currently existing and potential applications of this memory are primarily based on multicomponent alloys of metals and semiconductors. However single-component nanoparticles including Si ones are also of interest as promising nanosized memory cells. The potential for developing this type of memory cells is confirmed by the fact that the optical absorption index of bulk amorphous silicon is of the same order of magnitude as that of crystalline silicon. Certainly this phenomenon can hardly be implemented with a single nanoparticle the size of which is within light wavelength. Using molecular dynamics and the Stillinger-Weber potential we have studied the regularities of melting and the conditions of crystallization of silicon nanoparticles containing within 105 atoms. We have shown that cooling of nanosized silicon drops at a 0.2 TK/s rate or higher rates causes their amorphous transition whereas single-component nanosized metallic drops crystallize in molecular dynamics experiments even at a 1 TK/s rate. Further heating of amorphous silicon nanoparticles containing above 5 ∙ 104 atoms causes their crystallization in a specific temperature range from 1300 to 1400 K. We have concluded that there is a possibility of developing phase change memory cells on the basis of the above phase transitions. An amorphous transition of a nanoparticle can be achieved by its melting and further cooling to room temperature at a 0.2 TK/s rate whereas a crystalline transition, by its heating to 1300–1400 K at a 0.2 TK/s rate followed by cooling. Results of molecular dynamics experiments suggest there is a minimum silicon nanoparticle size for which the development of phase change memory cells becomes theoretically impossible at a given temperature change rate. For a 0.2 TK/s temperature change rate this minimum size is 12.4 nm (number of atoms approx. 5 ∙ 104).

Mechanisms of Coalescence of Metallic Nanodroplets and Sintering of Metallic Nanoparticles

The regularities and mechanisms of coalescence of Au nanodroplets and sintering of solid Au nanoparticles are investigated using molecular dynamics experiments and some theoretical models. It is established that the characteristic time of coalescence τ is proportional to the radius r0 of the original nanodroplets. Both the conclusion and the quantitative estimations of the proportionality coefficient between τ and r0 agree with Frenkel’s theory (1946), yet this theory was proposed for describing the coalescence of macroscopic droplets.

The interaction between grain boundary and tool geometry in nanocutting of a bi-crystal copper

Anisotropy is one central influencing factor on achievable ultimate machined surface integrity of metallic materials. Specifically, grain boundary has a strong impact on the deformation behaviour of polycrystalline materials and correlated material removal at the microscale. In the present work, we perform molecular dynamics simulations and experiments to elucidate the underlying grain boundary-associated mechanisms and their correlations with machining results of a bi-crystal Cu under nanocutting using a Berkovich tool. Specifically, crystallographic orientations of simulated bi-crystal Cu with a misorientation angle of 44.1° are derived from electron backscatter diffraction characterization of utilized polycrystalline copper specimen. Simulation results reveal that blocking of dislocation motion at grain boundaries, absorption of dislocations by grain boundaries and dislocation nucleation from grain boundaries are operating deformation modes in nanocutting of the bi-crystal Cu. Furthermore, heterogeneous grain boundary-associated mechanisms in neighbouring grains lead to strong anisotropic machining behaviour in the vicinity of the grain boundary. Simulated machined surface morphology and machining force evolution in the vicinity of grain boundary qualitatively agree well with experimental results. It is also found that the geometry of Berkovich tool has a strong impact on grain boundary-associated mechanisms and resultant ploughing-induced surface pile-up phenomenon.

Self-Assembled Monolayers for the Polymer/Semiconductor Interface with Improved Interfacial Thermal Management.

Reliability and lifespan of highly miniaturized and integrated devices will be effectively improved if excessive accumulated heat can be quickly transported to heat sinks. In this study, both molecular dynamics (MD) simulations and experiments were performed to demonstrate that self-assembled monolayers (SAMs) have high potential in interfacial thermal management and can enhance thermal transport across the polystyrene (PS)/silicon (Si) interface, modeling the common polymer/semiconductor interfaces in actual devices. The influence of packing density and alkyl-chain length of SAMs is investigated. First, MD simulations show that the interfacial thermal transport efficiency of SAM is higher with high packing density. The interfacial thermal conductance (ITC) between PS and Si can be improved up to 127 ± 9 MW m-2 K-1, close to the ITC across the metal and semiconductor interface. At moderate packing density, the SAMs with less than eight carbon atoms in the alkyl chain show superior improvements over those with more carbons because of the assembled structure variation. Second, the time-domain thermoreflectance technique was employed to characterize the ITCs of a bunch of Al/PS/SAM/Si samples. C6-SAM enhances the ITC by fivefolds, from 11 ± 1 to 56 ± 17 MW m-2 K-1. The interfacial thermal management efficiency will weaken when the alkyl chain exceeds eight carbon atoms, which agrees with the ITC trend from MD simulations at moderate packing density. The relationship between the SAM morphology and interfacial thermal management efficiency is also discussed in detail. This study demonstrates the feasibility of molecular-level design for interfacial thermal management from both the theoretical calculation and experiment and may provide a new idea for improving the heat dissipation efficiency of microdevices.

Uniaxial Deformation and Crazing in Glassy Polymer-Grafted Nanoparticle Ultrathin Films.

The deformation behavior of neat, glassy polymer-grafted nanoparticle (PGN) monolayer films is studied using coarse-grained molecular dynamics simulations and experiments on polystyrene-grafted silica. In both the simulations and experiments, apparent crazing behavior is observed during deformation. The PGN systems show a relatively more uniform, perforated sheet craze structure and significantly higher strain at break than reference homopolymers of the same length. Short chain, unentangled PGN monolayers are also simulated for comparison; these are brittle and break apart without crazing. The entangled PGN simulations are analyzed in detail for systems at both high and moderate graft density. Stress-strain curves show three distinct regions: yielding and strain localization, craze widening, and strain hardening preceding catastrophic failure. The PGN stress-strain behavior appears more similar to that of longer chain, highly entangled homopolymer films than to the reference homopolymer films of the same length as the graft chains, suggesting that the particles effectively add additional entanglement points. The moderate graft density particles have higher strain-to-failure and maximum stress than the high graft density particles. We suggest this increased robustness for lower graft density systems is due to their increased interpenetration of graft chains between neighboring particles, which leads to increased interparticle entanglements per chain.

Mechanism of Water Content on the Electrochemical Surface Area of the Catalyst Layer in the Proton Exchange Membrane Fuel Cell

Combined molecular dynamics (MD) simulation and experiment are adopted to gain the mechanism of water content on the electrochemical surface area (ECSA) of the catalyst layer in a proton exchange membrane fuel cell. The morphology of water domains in the catalyst layer has a strong impact on the ECSA via MD simulation. The morphology of the water domains is isolated water clusters at low water content, resulting in the poor ECSA due to the lack of proton transport paths. The transport paths of protons tend to be quickly established with increasing water content during the transition process of the morphology of water domains from isolated water clusters to the water channel network, thereby leading to the rapid increase of the ECSA. However, the slight increase of the ECSA at high water content mainly results from the improved contact area between water domains and Pt particle instead of the formation of new transport paths. In addition, the stronger binding of water molecules and the Pt particle at low temperature results in a higher ECSA.

Analysis of the Adsorption of Gases and Vapors on Carbon Surfaces Using the Molecular Dynamics Method

A molecular dynamic experiment is carried out for analyzing the isotherms of adsorption on a graphene surface at temperatures below and above the critical values for adsorptives. It is shown that the monomolecular isotherms of gas adsorption on the flat carbon surfaces can be described using the set of equations of the lattice model and the equations of the theory of the volume filling of micropores (TVFM). The obtained results are compared with the experimental data on adsorption in micropores of active carbons. When describing the isotherms of polymolecular adsorption with the use of the BET and the Aranovich equations, the filling of each layer is analyzed.

Effect of Layer Charge Density on Hydration Properties of Montmorillonite: Molecular Dynamics Simulation and Experimental Study.

Four kinds of Ca-montmorillonite with different layer charge density were used to study the effect of charge density on their hydration properties by molecular dynamics simulation and experiments. The research results of Z-density distribution of water molecules, Hw (hydrogen in water molecules), and Ca in the interlayer of montmorillonite show that the hydration properties of montmorillonite are closely related to its layer charge density. If the charge density is low, the water molecules in the interlayers are mainly concentrated on the sides of the central axis about –1.3 Å and 1.5 Å. As the charge density increases from 0.38semi-cell to 0.69semi-cell, the water molecules are distributed −2.5 Å and 2.4 Å away from the siloxane surface (Si-O), the concentration of water molecules near the central axis decreases, and at the same time, Ca2+ appears to gradually shift from the vicinity of the central axis to the Si-O surface on both sides in the montmorillonite layer. The simulation results of the radial distribution function (RDF) of the Ca-Hw, Ca-Ow (oxygen in water molecules), and Ca-Ot (the oxygen in the tetrahedron) show that the Ca2+ and Ow are more tightly packed together than that of Hw; with the increase of the charge density, due to the fact that the negative charge sites on the Si-O surface increase, under the action of electrostatic attraction, some of the Ca2+ are pulled towards the Si-O surface, which is more obvious when the layer charge density of the montmorillonite is higher. The results of the RDF of the Ot-Hw show that with the increase of charge density, the number of hydrogen bonds formed by Ot and Hw in the interlayers increase, and under the action of hydrogen bonding force, the water molecules near the central axis are pulled towards the two sides of Si-O surface. As a result, the arrangement of water molecules is more compact, and the structure is obvious. Correspondingly, the self-diffusion coefficient shows that the higher the layer charge density, the lower the self-diffusion coefficient of water molecules in interlayers is and the worse the hydration performance of montmorillonite. The experimental results of the experiments fit well with the above simulation results.

Comprehensive molecular dynamics studies of the ballistic resistance of multilayer graphene-polymer composite

Unlike most existing works, where the focus has been to study the ballistic performance of single and multilayer graphene sheets, our research is concerned with the ballistic behaviour of multilayer graphene polymer composite (MGPC). Specifically, the graphene membranes are embedded in polyethylene at varied depth and subjected to impingement by spherical projectiles traveling at varied translational velocities and impact angles. We conducted unique molecular dynamics experiments to predict the atomistic energy dissipation mechanisms of MGPC accounting for projectile spin. Three aspects of the study were considered: (i) examined the ballistic impact resistance of various MGPCs, (ii) established the energy dissipation mechanisms under supersonic impact, and (iii) determined the influence of projectile spin and impact angle on the ballistic resistance of MGPC. Our results reveal that a single layer of graphene membrane improves the ballistic impact resistance of polyethylene by over eight folds. Moreover, depending on the projectile velocity and the graphene arrangement, three distinct energy dissipation mechanisms were observed. The study further reveals that the spin of the projectile remarkably reduces the reactive force experienced by the projectile. These results provide novel insights into the energy dissipation mechanisms at the atomic scale.

Study of Si Surface Adsorption Towards Hydrogen Molecule

Recent approaches to address more efficient method on storing hydrogen by using adsorbent materials has been done. The hydrogen adsorption on silicon has been studied through molecular dynamics simulations and experiment by researchers. We conducted molecular dynamics simulation using a Lennard-Jones potential to demonstrate the hydrogen adsorption capability of silicon surface (001) and (111) with various temperature applied. The amount of hydrogen adsorbed by silicon surfaces are higher as entropy of the system decreases. Without considering entropy, Si (111) has higher adsorption capability due to its lower energy surface than Si (001).

The missing link: allostery and catalysis in the anti-viral protein SAMHD1.

Vertebrate protein SAMHD1 (sterile-α-motif and HD domain containing protein 1) regulates the cellular dNTP (2′-deoxynucleoside-5′-triphosphate) pool by catalysing the hydrolysis of dNTP into 2′-deoxynucleoside and triphosphate products. As an important regulator of cell proliferation and a key player in dNTP homeostasis, mutations to SAMHD1 are implicated in hypermutated cancers, and germline mutations are associated with Chronic Lymphocytic Leukaemia and the inflammatory disorder Aicardi–Goutières Syndrome. By limiting the supply of dNTPs for viral DNA synthesis, SAMHD1 also restricts the replication of several retroviruses, such as HIV-1, and some DNA viruses in dendritic and myeloid lineage cells and resting T-cells. SAMHD1 activity is regulated throughout the cell cycle, both at the level of protein expression and post-translationally, through phosphorylation. In addition, allosteric regulation further fine-tunes the catalytic activity of SAMHD1, with a nucleotide-activated homotetramer as the catalytically active form of the protein. In cells, GTP and dATP are the likely physiological activators of two adjacent allosteric sites, AL1 (GTP) and AL2 (dATP), that bridge monomer–monomer interfaces to stabilise the protein homotetramer. This review summarises the extensive X-ray crystallographic, biophysical and molecular dynamics experiments that have elucidated important features of allosteric regulation in SAMHD1. We present a comprehensive mechanism detailing the structural and protein dynamics components of the allosteric coupling between nucleotide-induced tetramerization and the catalysis of dNTP hydrolysis by SAMHD1.

Discovery of novel N-methyl carbazole tethered rhodanine derivatives as direct inhibitors of Mycobacterium tuberculosis InhA.

InhA (Enoyl-ACP reductase) plays a crucial role in the biosynthetic pathway of cell wall synthesis in Mycobacterium tuberculosis (Mtb). Isoniazid (INH) is an important first-line drug, which inhibits InhA. The rapid increase in resistance to INH and currently marketed drugs as well as emergence of MDR-TB and XDR-TB has complicated the diagnosis and treatment of Mtb with ever increasing threat to human kind. Herein, we report novel N-methyl carbazole derivatives as potential anti-TB compounds acting directly via InhA inhibition. All the synthesized final compounds were screened against Mtb virulent cell line H37Rv and investigated the InhA enzyme inhibition. Interestingly, compound 9e displayed promising inhibition (91%) at 50 µM concentration and IC50 of 2.82 µM against InhA. To understand the ligand receptor interaction between compound 9e and InhA, molecular docking and molecular dynamics experiments were performed. The computational results were in agreement with the observed experimental data. Further, the cytotoxicity studies on mammalian cells revealed that all the compounds were safe.

Nephroprotective activity of Combretum micranthum G. Don in cisplatin induced nephrotoxicity in rats: In-vitro, in-vivo and in-silico experiments

Nephrotoxicity is known to be a major complication during cisplatin chemotherapy in cancer patients. In the present study, the protective effect of a hydroalcoholic extract of Combretum micranthum (CM) against cisplatin (CP)-induced renal damage was evaluated using in-vitro human embryonic kidney (HEK)-293 cells and in-vivo experiments. Further, in-silico molecular docking and dynamic experiments were carried out with bioactive compounds of the title plant against nuclear factor kappa B (NF-κB) and soluble epoxide hydrolase (sEH). Incubation of HEK-293 cells with cisplatin resulted in a significant increase in cell death with changes in normal cellular morphology. Co-treatment of HEK-293 cells with CP and CM extract at varying concentrations resulted in significant enhancement of cell growth compared to CP treatment indicating the cytoprotective activity of CM with an EC50 8.136 μg/mL. In vivo nephroprotective activity was evaluated by administering CM (200 and 400 mg/kg, p.o) to rats for 10 days followed by single intraperitonial injection of CP (7.5 mg/kg) on the 5th day of the experiment. Nephrotoxicity induced by CP was apparent by elevated levels of serum and urine kidney function markers, transaminases, oxidative stress markers and histopathological alterations in kidney. Pre-treatment with CM normalized the renal function at both the doses by ameliorating the CP-induced renal damage markers, oxidative stress and histopathological variations. In-silico studies showed that, out of the thirty bioactive compounds, isovitexin and gallic acid exhibited a higher docking score of −22.467, −21.167 kcal/mol against NF-κB. Cianidanol and epicatechin exhibited a higher docking score of −14.234, −14.209 kcal/mol against sEH. The protective effect of CM extract in CP-induced nephrotoxicity might be attributed to its antioxidant, anti-inflammatory activity by inhibiting NF-κB and sEH upregulation.

Wettability of Primer-Treated Al2O3 Surfaces by Bisphenol A Diglycidyl Ether: Determination of the Mechanism from Molecular Dynamics Simulations and Experiments.

This study aims to develop a molecular dynamics (MD) simulation procedure to investigate the wettability of primer-treated Al2O3 surfaces by bisphenol A diglycidyl ether (BADGE) and to understand the interaction between the surface and the liquid. The MD simulation results were compared with those obtained by contact angle measurements, time-of-flight secondary ion mass spectrometry (TOF-SIMS), and atomic force microscopy (AFM) and were found to be in agreement with the experimental evaluations. The results obtained from both the MD simulations and the experiments suggest that the configuration of the primers on the surface affect its wettability. In other words, silanes lying flat on the surface, such as mercapto silane, make it easy for BADGE to access any polar functional groups of the silane, thereby leading to a strong interaction and good wettability. For amino silane, although the configuration is similar to that of mercapto silane, its amino groups are bound to the surface owing to their high polarity, which results in a reduced accessibility for BADGE and a relatively poor wettability in comparison with mercapto silane. On the contrary, for silanes that stand up on the surface, including trifluoroalkyl silane, BADGE is hindered from approaching the silanol groups and interacting with them, and the surface shows poor wettability.

Adsorption of Gadolinium (Gd3+) Ions on the Dibenzo Crown Ether (DBCE) and Dicyclo Hexano Crown Ether (DCHCE) Grafted on the Polystyrene Surface: Insights from All Atom Molecular Dynamics Simulations and Experiments

All atom molecular dynamics simulations and experiments were performed to understand the adsorption behavior of gadolinium (Gd3+) ion on the crown ethers grafted polystyrene (PS) surface. Two different types of crown ethers, viz., dibenzo crown ether (DBCE) and dicyclo hexano crown ether (DCHCE), were grafted separately on the PS surface to understand the adsorption behavior. We investigate the roles of Gd3+ ion concentration and grafting density (ρs) of the crown ether on the adsorption behavior of Gd3+ ion on the PS surface. The adsorption of Gd3+shows an increasing trend with increasing salt concentration, for all cases of crown ether grafting densities. The adsorption behavior follows the Langmuir isotherm model. The maximum amount of Gd3+ ion adsorption was observed to be 1.83 mg/g for DBCE and 2.02 mg/g for DCHCE at ρs = 2.07 mol/nm2. The maximum amount of Gd3+ ion adsorption on DBCE coated PS beads, in batch experiments, was found to be 1.76 mg/g, which is in good agreement with the theoretical res...

Calcium ion effects on the water/oil interface in the presence of anionic surfactants

The influence of ion type at constant ionic strength on the surfactant layer present between a polar and a non-polar liquid has been investigated. The investigated systems are composed of sodium bis(2-ethylhexyl) sulfosuccinate (AOT), dodecane and brines with different electrolyte compositions. Parallel and coordinated sampling have been performed via molecular dynamics simulation and experiments. By varying the molar ratio between calcium and sodium ions at constant ionic strength, we determined the relative influence of the bivalent ion. In the present work, firstly, we provide an atomistic description via molecular dynamics (MD) simulations of the surfactant and electrolyte distributions in respect to the dodecane-water interface. Secondly, we report the interfacial tension (IFT) and the estimated Debye length based on the theory of the electric double layer, comparing the simulation results with a classical interface description.

Anthranilic Acid Inhibitors of Undecaprenyl Pyrophosphate Synthase (UppS), an Essential Enzyme for Bacterial Cell Wall Biosynthesis.

We report the successful implementation of virtual screening in the discovery of new inhibitors of undecaprenyl pyrophosphate synthase (UppS) from Escherichia coli. UppS is an essential enzyme in the biosynthesis of bacterial cell wall. It catalyzes the condensation of farnesyl pyrophosphate (FPP) with eight consecutive isopentenyl pyrophosphate units (IPP), in which new cis-double bonds are formed, to generate undecaprenyl pyrophosphate. The latter serves as a lipid carrier for peptidoglycan synthesis, thus representing an important target in the antibacterial drug design. A pharmacophore model was designed on a known bisphosphonate BPH-629 and used to prepare an enriched compound library that was further docked into UppS conformational ensemble generated by molecular dynamics experiment. The docking resulted in three anthranilic acid derivatives with promising inhibitory activity against UppS. Compound 2 displayed high inhibitory potency (IC50 = 25 μM) and good antibacterial activity against E. coli BW25113 ΔtolC strain (MIC = 0.5 μg/mL).

Computational investigation of mechanistic insights of Aβ42 interactions against extracellular domain of nAChRα7 in Alzheimer’s disease

Aim: Amyloid beta (Aβ) 1-42, which is a basic constituent of amyloid plaques, binds with extracellular transmembrane receptor nicotine acetylcholine receptor α7 (nAChRα7) in Alzheimer’s disease.Materials and Methods: In the current study, a computational approach was employed to explore the active binding sites of nAChRα7 through Aβ 1–42 interactions and their involvement in the activation of downstream signalling pathways. Sequential and structural analyses were performed on the extracellular part of nAChRα7 to identify its core active binding site.Results: Results showed that a conserved residual pattern and well superimposed structures were observed in all nAChRs proteins. Molecular docking servers were used to predict the common interactive residues in nAChRα7 and Aβ1–42 proteins. The docking profile results showed some common interactive residues such as Glu22, Ala42 and Trp171 may consider as the active key player in the activation of downstream signalling pathways. Moreover, the signal communication and receiving efficacy of best-docked complexes was checked through DynOmic online server. Furthermore, the results from molecular dynamic simulation experiment showed the stability of nAChRα7. The generated root mean square deviations and fluctuations (RMSD/F), solvent accessible surface area (SASA) and radius of gyration (Rg) graphs of nAChRα7 also showed its backbone stability and compactness, respectively.Conclusion: Taken together, our predicted results intimated the structural insight on the molecular interactions of beta amyloid protein involved in the activation of nAChRα7 receptor. In future, a better understanding of nAChRα7 and their interconnected proteins signalling cascade may be consider as target to cure Alzheimer’s disease.

Revisiting the Rayleigh–Plateau instability for the nanoscale

The theoretical framework developed by Rayleigh and Plateau in the 19th century has been remarkably accurate in describing macroscale experiments of liquid cylinder instability. Here we re-evaluate and revise the Rayleigh–Plateau instability for the nanoscale, where molecular dynamics experiments demonstrate its inadequacy. A new framework based on the stochastic lubrication equation is developed that captures nanoscale flow features and highlights the critical role of thermal fluctuations at small scales. Remarkably, the model indicates that classically stable (i.e. ‘fat’) liquid cylinders can be broken at the nanoscale, and this is confirmed by molecular dynamics.