Non-bonded Energy Research Articles

Effects of Nanoparticles’ Size and Shape on the Thermodynamic Properties of PI/SiO2 Nanocomposites

In this paper, the effects of SiO2 size (ranging from 5.7[Formula: see text]Å to 7.50[Formula: see text]Å) and shape (spherical, cylindrical and rod) on the interface structure and the thermodynamic performance of polyimide (PI)/SiO2 composites were investigated by molecular dynamics simulation. Also, whether the nanofiller with isocyanate propyl triethoxysilane (ICTOS) can highly enhance interaction in PI/SiO2 (bonded PI/SiO[Formula: see text] was investigated by experiment. To enhance the interfacial intensity efficiency, the coupling agent ICTOS was used to modify the surface of the silica nanoparticle. The results showed that the size and shape of SiO2 not only affect the interfacial number of hydrogen bonds and the interfacial area, but also impact on the glass transition temperature of the composites. As the radius of the embedded nanosilica increased, the bonded energy and [Formula: see text] gradually decreased, showing a prominent filler size effect. At the same time, the [Formula: see text] of spherical-type system was significantly greater than the nanosystems of other shapes. This is because as the number of surface atoms and superficial area of the spherical filler are higher than the nanofillers of other shapes, the combination between spherical-type silica and the PI chains is more compact than those between cylindrical and rod-like silica and the PI chains. The contributions of different nanofillers to the filler size dependency of [Formula: see text] of the nanocomposites can be elucidated by comparing the interfacial interaction and net structure between the PI matrix and silica which exhibit prominent filler shape and size dependency. Finally, the results were confirmed by the nonbonded interaction energy and reduced radial distribution function (RRDF), and the highly interaction interface is found to bring about a greater reinforcing effect.

Excess molar volumes of cyclohexanone with n-, sec-, or tert-butylbenzene: Application of the PFP theory and graph-theoretical approach

Excess molar volumes, VE, for the binary mixtures of cyclohexanone with n-, sec-, or tert-butylbenzene were measured over the entire composition range at (298.15, 303.15, 308.15 and 313.15) K and 0.1 MPa, by means of a vibrating-tube densimeter. VE data are sigmoid shape for the studied mixtures of cyclohexanone + n-butylbenzene (with negative VE values at lower mole fractions of cyclohexanone) and negative for the mixtures of cyclohexanone + sec-butylbenzene, and cyclohexanone + tert-butylbenzene over the whole composition range. The absolute values of excess equimolar volumes vary in the order: tert-butylbenzene > sec-butylbenzene > n-butylbenzene. The VE in the studied systems increase as the rising temperature. The Redlich-Kister equation was applied to fit the experimental data. Using the coefficients of the Redlich–Kister equation, excess partial molar volumes at infinite dilution, V¯iE,∞ were calculated for the three binary systems. Molecular non-bond energy, E for binary mixtures at the mole fraction of 0.5 and temperature of 298.15 K also were calculated by the MD simulations. The Prigogine–Flory–Patterson theory and Graph-theoretical approach were examined for the suitability by correlating experimental VE data with compositions.

Quantum-Chemical and Experimental Estimation of Non-Bonding Level (Fermi Level) and π-Electron Afinity of Conjugated Systems

Method of quantitative estimation of the π-electron affinity for conjugated molecules, which is directly related to donor/acceptor properties is presented. The index φ0 is proposed, it is determined by disposition of the frontier levels in respect to the non-bonding π-level (Fermi level). It is shown that this index/parameter can be estimated not only by quantum-chemical calculation, but also experimentally using the ionization potentials and electron affinity or/and the electron transition energy. The non-bonding level energy can be estimated basing on the parity theorem: in the alternant conjugated molecules, the occupied and vacant levels (including the highest occupied and lowest vacant levels) are disposed symmetrically in respect to the non-bonding levels. The proposed parameter is convenient for quantitative analysis of the donor/acceptor properties as well as the affinity of any conjugated molecule.

Dual responsive PMEEECL-PAE block copolymers: a computational self-assembly and doxorubicin uptake study.

The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens–Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20–AEM compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (Tcg) of these copolymers and finding appropriate CG mapping for both PMEEECL–PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75–80%) at different concentrations inside the PMEEECL–PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL–PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.

Understanding Creep Behavior of Semicrystalline Polymer via Coarse‐Grained Modeling

ABSTRACTUnderstanding the deformational and failure behaviors of thermoplastic semicrystalline polymers is crucial due to the practical usages in various engineering applications. Taking isotactic polypropylene (iPP) as a semicrystalline polymer model system, atomistically informed coarse‐grained (CG) molecular dynamics (MD) simulations are employed to investigate the creep behavior of iPP. The simulations reveal that there exists a threshold stress of about 20.0 MPa, above which the maximum strain of iPP within the simulation time span increases dramatically. From the strain‐time analysis, it is observed that the iPP exhibits an initial elastic deformation stage and a subsequent plastic stage at lower stress levels, while a three‐stage creep behavior including a third fracture stage is observed at higher stress levels. Specifically, at lower stress levels, the bonded energy increases continuously as the chains stretch steadily, while the nonbonded energy shows an initial increase followed by a steady decrease due to the interchain sliding. At higher stress levels, both bonded and nonbonded energies change dramatically at the third stage, resulting from accelerated chain stretching, unfolding, sliding, and breaking. This study provides physical insight into the creep behavior of iPP at a fundamental molecular level and highlights the important role of microstructural evolution of chains in the deformation of semicrystalline polymer materials. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 1779–1791

The Effect of Temperature and Strain Rate on the Interfacial Behavior of Glass Fiber Reinforced Polypropylene Composites: A Molecular Dynamics Study.

To make better use of fiber reinforced polymer composites in automotive applications, a clearer knowledge of its interfacial properties under dynamic and thermal loadings is necessary. In the present study, the interfacial behavior of glass fiber reinforced polypropylene (PP) composites under different loading temperatures and strain rates were investigated via molecular dynamics simulation. The simulation results reveal that PP molecules move easily to fit tensile deformation at higher temperatures, resulting in a lower interfacial strength of glass fiber–PP interface. The interfacial strength is enhanced with increasing strain rate because the atoms do not have enough time to relax at higher strain rates. In addition, the non-bonded interaction energy plays a crucial role during the tensile deformation of composites. The damage evolution of glass fiber–PP interface follows Weibull’s distribution. At elevated temperatures, tensile loading is more likely to cause cohesive failure because the mechanical property of PP is lower than that of the glass fiber–PP interface. However, at higher strain rates, the primary failure mode is interfacial failure because the strain rate dependency of PP is more pronounced than that of the glass fiber–PP interface. The relationship between the failure modes and loading conditions obtained by molecular dynamics simulation is consistent with the author’s previous experimental studies.

Transferable coarse-grained models for poly(ethylene oxide)/poly(methyl methacrylate) blends

The recently developed multiscale scheme has been extended to parameterize the coarse-grained (CG) potentials for simulating the two binary blends comprised of poly(ethylene oxide) (PEO) and isotactic or syndiotactic poly(methyl methacrylate) (iPMMA, sPMMA). The specific volumes and the non-bonded interaction energies reveal a single glass transition temperature (Tg), and the dynamical Tg and chain dimension exhibit a strong composition-dependence, and the scale-dependent miscibility is confirmed. As inferred from the intermolecular radial distribution function (RDF), sPMMA is more miscible with PEO than is iPMMA. For any of these systems, the heats and free energies of mixing are most negative at the middle composition. More negative free energy of mixing at lower temperature predicts a lower critical solution temperature. All these simulated results are in good agreements with the experimental observations, validating the multiscale scheme with the ability to derive the transferable CG potentials.

Molecular Dynamics Simulation on the Influences of Nanostructure Shape, Interfacial Adhesion Energy, and Mold Insert Material on the Demolding Process of Micro-Injection Molding

In micro-injection molding, the interaction between the polymer and the mold insert has an important effect on demolding quality of nanostructure. An all-atom molecular dynamics simulation method was performed to study the effect of nanostructure shape, interfacial adhesion energy, and mold insert material on demolding quality of nanostructures. The deformation behaviors of nanostructures were analyzed by calculating the non-bonded interaction energies, the density distributions, the radii of gyration, the potential energies, and the snapshots of the demolding stage. The nanostructure shape had a direct impact on demolding quality. When the contact areas were the same, the nanostructure shape did not affect the non-bonded interaction energy at PP-Ni interface. During the demolding process, the radii of gyration of molecular chains were greatly increased, and the overall density was decreased significantly. After assuming that the mold insert surface was coated with an anti-stick coating, the surface burrs, the necking, and the stretching of nanostructures were significantly reduced after demolding. The deformation of nanostructures in the Ni and Cu mold inserts were more serious than that of the Al2O3 and Si mold inserts. In general, this study would provide theoretical guidance for the design of nanostructure shape and the selection of mold insert material.

Micro-scale effects of nano-SiO2 modification with silane coupling agents on the cellulose/nano-SiO2 interface

In this study, molecular dynamics simulations were used to investigate the micro-scale effects of modification of nano-SiO2 with commonly used silane coupling agents (KH550, KH560, KH570, and KH792) on the cellulose/nano-SiO2 interface. The relative optimum silane coupling agent and grafting density for nano-SiO2 modification to improve the cellulose/nano-SiO2 interface were determined. The results showed that at the same grafting density, modification of nano-SiO2 with KH792 yielded the highest interfacial binding energy and binding energy density, the largest number of hydrogen bonds at the cellulose/nano-SiO2 interface, the strongest binding to the cellulose chains, and the largest overlapping area at the cellulose/nano-SiO2 interface. We found that the non-bonding interaction energy played a decisive role in the energy of the model system and the interfacial interaction force mainly consisted of van der Waals forces and the hydrogen-bonding energy. When silane coupling agents with amino groups (KH550 and KH792) were used to modify nano-SiO2, the number of hydrogen bonds at the cellulose/nano-SiO2 interface was larger than that for unmodified nano-SiO2. When silane coupling agents without amino groups (KH560 and KH570) were used to modify nano-SiO2, the number of hydrogen bonds at the cellulose/nano-SiO2 interface was lower than the case for unmodified nano-SiO2. Nano-SiO2 modification with various amounts of KH792 was investigated. The results showed that the interfacial bonding energy increased with grafting density. When the grafting density was 1.57 nm−2, the interfacial bonding energy and number of hydrogen bonds formed at the cellulose/nano-SiO2 interface was relatively stable, which indicates that the interface had reached a relatively stable state. Modification of nano-SiO2 with KH792 achieved the greatest improvement of the cellulose/nano-SiO2 interface; this interface reached a relatively stable state when the grafting density of KH792 was 1.57 nm−2.

In silico study of α-γ phase transformation in hexahydro-1,3,5-trinitro-1,3,5-triazine

Molecular dynamics (MD) simulations are performed using the Smith and Bharadwaj (SB) molecular potential to study the response of α-RDX to hydrostatic compression up to 4 GPa between 300 K and 450 K. We observe a phase transformation to the high-pressure γ polymorph around 2.5 GPa for temperatures greater than or equal to 350 K. The α-γ phase transformation is captured through an abrupt decrease in the ‘b’ lattice parameter and volume while the ‘c’ lattice parameter shows an abrupt increase. The molecular conformation is shown to evolve from AAE to AAE-AAI during the phase transition, consistent with experimental observations. Abrupt changes are also observed in molecular and non-bonded energy terms of the SB potential. The phase at the end of hydrostatic loading is verified to be γ-RDX. The simulations demonstrate that SB potential can be effective in further elucidating the deformation mechanisms in RDX compressed beyond the phase transition pressure. We hypothesize that the difference in angle energy between the two phases plays an important role in the occurrence of α-γ phase transformation in RDX using the SB potential.

Physiochemical Properties and Molecular Dynamics Simulations of Phosphonium and Ammonium Based Deep Eutectic Solvents

Deep eutectic solvents (DES) are considered as second-generation ionic liquids and are used in many applications such as separation, extraction and electrochemistry. In the current work, a set of four DES is synthesized by mixing a hydrogen bond donor (HBD) (ethylene glycol/glycerol) with a quaternary ammonium or phosphonium salt or the hydrogen bond acceptor (HBA). Here the HBA, namely methyltriphenylphosphonium bromide and tetrabutylammonium bromide (TBAB), were mixed with the HBD in a molar ratio of 1:4. Fourier transform infrared and thermogravimetric analysis analysis were then carried out to understand the functional groups along with their thermal stability. NMR analysis was also used to validate the molar ratio of 1:4 in solution. Thereafter, the four DESs were simulated with molecular dynamics simulations to evaluate and measure the pure component properties of these solvents at room temperature. Thermodynamics insights such as non-bonded interaction energies, hydrogen bonds, coordination number and radial distribution functions were also discussed to understand their atomistic interactions involved in the eutectic mixtures.

Spectral analysis of molecular dynamics simulations on PDZ: MD sectors

The idea of protein “sectors” posits that sparse subsets of amino acid residues form cooperative networks that are key elements of protein stability, ligand binding, and allosterism. To date, protein sectors have been calculated by the statistical coupling analysis (SCA) method of Ranganathan and co-workers via the spectral analysis of conservation-weighted evolutionary covariance matrices obtained from a multiple sequence alignments of homologous families of proteins. SCA sectors, a knowledge-based protocol, have been indentified with functional properties and allosterism for a number of systems. In this study, we investigate the utility of the sector idea for the analysis of physics-based molecular dynamics (MD) trajectories of proteins. Our test case for this procedure is PSD95- PDZ3, one of the smallest proteins for which allosterism has been observed. It has served previously as a model system for a number of prediction algorithms, and is well characterized by X-ray crystallography, NMR spectroscopy and site specific mutagenisis. All-atom MD simulations were performed for a total of 500 nanoseconds using AMBER, and MD-calculated covariance matrices for the fluctuations of residue displacements and non-bonded interaction energies were subjected to spectral analysis in a manner analogous to that of SCA. The composition of MD sectors was compared with results from SCA, site specific mutagenesis, and allosterism. The concordance indicates that MD sectors are a viable protocol for analyzing MD trajectories and provide insight into the physical origin of the phenomenon.Communicated by Ramaswamy H. Sarma

Natural ACE inhibitory peptides discovery from Spirulina (Arthrospira platensis) strain C1

Bioactive peptides from natural sources are utilized as food supplements for disease prevention and are increasingly becoming targets for drug discovery due to their specificity, efficacy and the absence of undesirable side effects, among others. Hence, the ‘SpirPep’ platform was developed to facilitate the in silico-based bioactive peptide discovery of these highly sought-after biomolecules from Spirulina(Arthrospira platensis) and to select the protease (thermolysin) used for in vitro digestion. Analysis of the predicted and experimentally-derived peptides suggested that they were mainly involved in ACE inhibition; thus, an ACEi assay was used to study the ACE inhibitory activity of five candidate peptides (SpirPep1-5), chosen from common peptides with multifunctional bioactivity and 100% bioactive peptide coverage, originating from phycobiliproteins. Results showed that SpirPep1 inhibited the activity of ACE with IC50 of 1.748 mM and was non-toxic to fibroblasts of African green monkey kidney and human dermal skin. The molecular docking and MD simulation analysis revealed SpirPep1 had significantly lower binding scores than others and showed greater specificity to ACE. The non-bonded interaction energy of SpirPep1 and ACE was −883 kJ/mol. The SpirPep1 indirectly bound to ACE via the ACE substrate binding sites residues (D121, E123, S516, and S517) found in natural ACE inhibitory peptides (angiotensin II and bradykinin potentiating peptides). In addition, two unreported substrate binding sites including R124 and S219 were found. These results indicate that ‘SpirPep’ platform could increase the success rate for natural bioactive peptide discovery.

Deformation modeling of polyamide 6 and the effect of water content using molecular dynamics simulation

Polyamide 6 (PA6) shows significant water absorbability and hygroscopicity, which affect its mechanical properties such as Young’s modulus and yield strength, as water content enhances deformability. This study aims to investigate the effect of water molecules on the deformation behavior of PA6 and to elucidate the deformation mechanism at a molecular level. By using excluded volume map sampling method, we explored the possible incursion sites for water molecule absorption in the computational material cell. Using molecular dynamic simulations, we created the computational cell of PA6, and we applied mechanical loadings with and without the water molecule to determine the effect of water molecules on the deformation behavior. To investigate the fundamental reasons why water molecules enhance the deformability of PA6, we calculated the non-bonded potential energy of a pair of amide functional groups with and without the water molecule. The results reveal that water molecules decrease the interaction energy of the amide group, leading to macroscopic deformation. This study clarified the effect of water molecules on the deformation behavior of PA6, and it may be useful for predicting the mechanical deformation of PA6.

Unraveling the metastability of the SI and SII carbon monoxide hydrate with a combined DFT-neutron diffraction investigation.

Clathrate hydrates are crystalline compounds consisting of water molecules forming cages (so-called "host") inside of which "guest" molecules are encapsulated depending on the thermodynamic conditions of formation (systems stable at low temperature and high pressure). These icelike systems are naturally abundant on Earth and are generally expected to exist on icy celestial bodies. Carbon monoxide hydrate might be considered an important component of the carbon cycle in the solar system since CO gas is one of the predominant forms of carbon. Intriguing fundamental properties have also been reported: the CO hydrate initially forms in the sI structure (kinetically favored) and transforms into the sII structure (thermodynamically stable). Understanding and predicting the gas hydrate structural stability then become essential. The aim of this work is, thereby, to study the structural and energetic properties of the CO hydrate using density functional theory (DFT) calculations together with neutron diffraction measurements. In addition to the comparison of DFT-derived structural properties with those from experimental neutron diffraction, the originality of this work lies in the DFT-derived energy calculations performed on a complete unit cell (sI and sII) and not only by considering guest molecules confined in an isolated water cage (as usually performed for extracting the binding energies). Interestingly, an excellent agreement (within less than 1% error) is found between the measured and DFT-derived unit cell parameters by considering the Perdew-Burke-Ernzerhof (denoted PBE) functional. Moreover, a strategy is proposed for evaluating the hydrate structural stability on the basis of potential energy analysis of the total nonbonding energies (i.e., binding energy and water substructure nonbonding energy). It is found that the sII structure is the thermodynamically stable hydrate phase. In addition, increasing the CO content in the large cages has a stabilizing effect on the sII structure, while it destabilizes the sI structure. Such findings are in agreement with the recent experimental results evidencing the structural metastability of the CO hydrate.

Molecular dynamics study of HDAC8-largazole analogues co-crystals for designing potential anticancer compounds

The X-ray crystal structures of HDAC8 complexed with largazole thiol (LAR, PubChem CID: 56663191) and its synthetic variants (Ligand ID in PDB, PubChem CID: L6G, 91667418; L7G, 91667421; L8G, 91667420) (PDB codes: 3RQD, 4RN0, 4RN2 and 4RN1) were analyzed using molecular dynamics simulations to comprehend protein-ligand nonbonding energies (NBEs). The NBEs of ligands’ substructures vis-à-vis active site indicated that pyridyl fragment (F2B4) in L7G and L8G, and amide fragment (F2B5) in LAR and L6G are in high energy states. Based on ligands’ substructures and active site residues properties new compounds were designed by introducing phenolic and amidine moieties, respectively, for F2B4 and F2B5. This improved NBEs of new compounds (NC2, –60.93 kcal/mol; NC3, -42.42 kcal/mol). Also, Zn2+ group (substructure F1) of largazoles was modified with that of SAHA and Trapoxin A. Here, the results indicated in favor of Zn2+ group of Trapoxin A. New compound NC6 incorporating aforesaid modifications i.e. phenolic moiety for F2B4, amidine moiety for F2B5 and Zn2+ group of Trapoxin A in F1, offered best interactions with HDAC8 (–89.75 kcal/mol). Thus, the study revealed new depsipeptides as potential HDAC8 inhibitors.AbbreviationsCAScomposite active siteCHARMMchemistry at Harvard Macromolecular MechanicsCUDAcompute unified device architectureHAThistone acetyletransferaseHDAChistone deacetylaseLARlargazole thiol (or) (2R,5R,8R,11R)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1 ∼ 2,5∼]icosa-1(18),16(19)-diene-6,9,13-trioneL6G(5R, 8S,11S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-3,17-dithia-7,10,14,19,20-pentaazatricyclo[14.2.1.1 ∼ 2,5∼]icosa-1(18),2(20),16(19)-triene-6,9,13-trione)L7G(5R,8S,11S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-3-thia-7,10,14,17,21-pentaazatricyclo[14.3.1.1 ∼ 2,5∼]henicosa-1(20),2 (21),16,18-tetraene-6,9,13-trioneL8G(5R,8S,11S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-3-thia-7,10,14,20,21-pentaazatricyclo[14.3.1.1 ∼ 2,5∼]henicosa-1(20),2(21),16,18-tetraene-6,9,13-trioneMDmolecular dynamicsMOEmolecular operating environmentNAMDnanoscale molecular dynamicsNBEnonbonding energyNBEEelectrostatic nonbonding energyNBEVVan der Waals nonbonding energyNBEFnonbonding energy of fragmentNBEFEelectrostatic nonbonding energy of fragmentNBEFVVan der Waals nonbonding energy of fragmentNCnew compound; Rg: radius of gyration;RMSDroot mean square deviationRMSFroot mean square fluctuationVMDvisual molecular dynamics.Communicated by Ramaswamy H. Sarma

Molecular dynamics simulation of water molecules adsorption by different cations based montmorillonite

Using molecular mechanics and molecular dynamics methods, Li-, Na-, K-, Ca-cations based montmorillonite models are built in Materials Studio software. After absorbing 16, 32, 48, 64, 80, 96 water molecules, geometry optimization is performed to get the optimum configuration, the influences of geometry optimization on the total energy of the system is analyzed. Further, molecular dynamic simulations are carried out to investigate the influences of different cations on the swelling behavior of montmorillonite when absorbing water. After geometry optimization, cations are moving close to the position of isomorphism substitution, the initial regular structure changed, the total energy of the system also changed greatly, the total energy of the system is reduced, both bond energy and non-bond energy are reduced, the reduction of the bond energy is about 56% of the reduced total energy. Torsional energy of dihedral angle is increased a bit, indicating the increased structural distortion. The bond stretching energy is reduced about 90%. Molecular dynamic simulations indicate the montmorillonite volume and layer spacing are increased by multi-steps, but the density is reduced by multi-steps. Water molecule concentration profiles in lithium-, sodium-, potassium- and calcium-montmorillonite adsorption models show that the montmorillonite can form one, two and three layers of water molecules. The radial distribution function of Li-, Na-, K-, Ca-cations based montmorillonite is obtained for absorbing 16 to 96 water molecules. The results indicate that Li+ is easier to hydrate, follows by Na+, while K+ and Ca2+ are not easy to hydrate. Different types of cations between layers have different effects on the adsorption ability of montmorillonite. After obtaining the mean squared distance of different cations and water molecules, the self-diffusion coefficients are calculated by fitting mean squared distance curves with the least square method. Compared with the literature data by Wang, Chang, and Na, it indicates that different cations, simulation methods, potential function, and simulation temperature all affect the diffusion of the middle layer cations and water molecules. MD simulations revealed the mechanism of chemical stabilization of expansive soils from molecular level.

Pharmacological and molecular dynamics analyses of differences in inhibitor binding to human and nematode PDE4: Implications for management of parasitic nematodes

Novel chemical controls are needed that selectively target human, animal, and plant parasitic nematodes with reduced adverse effects on the host or the environment. We hypothesize that the phosphodiesterase (PDE) enzyme family represents a potential target for development of novel nematicides and anthelmintics. To test this, we identified six PDE families present in the nematode phylum that are orthologous to six of the eleven human PDE families. We characterized the binding interactions of family-selective PDE inhibitors with human and C. elegans PDE4 in conjunction with molecular dynamics (MD) simulations to evaluate differences in binding interactions of these inhibitors within the PDE4 catalytic domain. We observed that roflumilast (human PDE4-selective inhibitor) and zardaverine (selective for human PDE3 and PDE4) were 159- and 77-fold less potent, respectively, in inhibiting C. elegans PDE4. The pan-specific PDE inhibitor isobutyl methyl xanthine (IBMX) had similar affinity for nematode and human PDE4. Of 32 residues within 5 Å of the ligand binding site, five revealed significant differences in non-bonded interaction energies (van der Waals and electrostatic interaction energies) that could account for the differential binding affinities of roflumilast and zardaverine. One site (Phe506 in the human PDE4D3 amino acid sequence corresponding to Tyr253 in C. elegans PDE4) is predicted to alter the binding conformation of roflumilast and zardaverine (but not IBMX) into a less energetically favorable state for the nematode enzyme. The pharmacological differences in sensitivity to PDE4 inhibitors in conjunction with differences in the amino acids comprising the inhibitor binding sites of human and C. elegans PDE4 catalytic domains together support the feasibility of designing the next generation of anthelmintics/nematicides that could selectively bind to nematode PDEs.

Molecular Dynamics Simulation on the Effect of Bonding Pressure on Thermal Bonding of Polymer Microfluidic Chip.

Thermal bonding technology is the most commonly used approach in bonding injection-molded microfluidic chips. Although the bonding mechanism is still under debate, the molecular dynamics (MD) method can provide insight into the bonding process on a macromolecular level. In this study, MD simulations for thermal bonding of PMMA substrate and cover sheet were performed. The molecule configuration and density distribution during the thermal bonding process were studied. The effects of bonding pressure on the equivalent strain, joining energy and diffusion coefficient were investigated. The debonding process was simulated to analyze the bonding strength and failure mechanism. Simulation results show that penetration mainly takes place near the interface area. Although the final density increases slightly with increasing pressure, the bonding interface is still insufficiently filled. The equivalent strain grows faster than that in the later stage because of the gap at the interface. The bonding pressure shows clear effects on the joining energy, diffusion coefficient and stress–strain behavior. Tensile failure occurs at the interface, with PMMA chains stretched between two layers. The majority of the change in potential energy is correlated with the change in non-bonded energy. At yield strain, the low-density defect at the interface weakens the tensile strength of bonded chip.

Dimerization energetics of curli fiber subunits CsgA and CsgB

Curli fibers are functional amyloids that exhibit strong adhesion and robust self-assembly as biofilm structural components; however, the binding energetics and mechanical properties of wild-type curli are not well understood. To address this, we present dimer structures made up of the major and minor curli subunits (CsgA and CsgB), perform free energy calculations to obtain absolute binding energies, and estimate the Young’s modulus and persistence length of curli fibers. Equilibrium molecular dynamics simulations are used to evaluate nonbonded interactions. Binding energies are most favorable for CsgB–CsgA, while CsgA–CsgA dimers have a higher binding energy than CsgB–CsgB despite possessing less favorable nonbonded interaction energies. Decomposing each potential of mean force of separation indicated that solvent effects positively impact CsgA–CsgA binding but not CsgB–CsgB and CsgB–CsgA. Charged residues and conserved polar residues were also notable contributors to attractive nonbonded interactions, underlining their importance in dimer assembly. Our findings elucidate sequence effects on binding energy contributions and establish theoretical limits for the elasticity, persistence length, and strength of curli fibers.