Search Results (25)

Polyethylene glycol (PEG) is one of the environmentally benign solvent options for green chemistry. It readily absorbs water when exposed to the atmosphere. The Molecular Dynamics (MD) simulations of PEG200, a commercial mixture of low molecular weight polyethyelene glycol oligomers, as well as di-, tetra-, and hexaethylene glycol are presented to study the effect of added water impurities up to a weight fraction of 0.020, which covers the typical range of water impurities due to water absorption from the atmosphere. Each system was simulated a total of four times using different combinations of two force fields for the water (SPC/E and TIP4P/2005) and two force fields for the PEG and oligomer (OPLS-AA and modified OPLS-AA). The observed trends in the effects of water addition were qualitatively quite robust with respect to these force field combinations and showed that the water does not aggregate but forms hydrogen bonds at most between two water molecules. In general, the added water causes overall either no or very small and nuanced effects in the simulation results. Specifically, the obtained water RDFs are mostly identical regardless of the water content. The added water reduces oligomer hydrogen bonding interactions overall as it competes and forms hydrogen bonds with the oligomers. The loss of intramolecular oligomer hydrogen bonding is in part compensated by oligomers switching from inter- to intramolecular hydrogen bonding. The interplay of the competing hydrogen bonding interactions leads to the presence of shallow extrema with respect to the water weight fraction dependencies for densities, viscosities, and self-diffusion coefficients, in contrast to experimental measurements, which show monotonous dependencies. However, these trends are very small in magnitude and thus confirm the experimentally observed insensitivity of these physical properties to the presence of water impurities. Full article

Polyimides feature a vast number of industrial applications due to their high thermal stability and insulation properties. These polymers exhibit an exceptional combination of thermal stability and mechanical toughness, which allows the semiconductor industry to use them as a mechanical stress buffer. Here, we perform all-atom molecular dynamics (MD) simulations for such materials to assess their predictive capability with respect to their mechanical properties. Specifically, we demonstrate that the OPLS-AA force field can be used to successfully describe an often-used polyimide (i.e., Kapton^®) with respect to its Young’s modulus and Poisson’s ratio. Two different modes to extract these mechanical properties from MD simulations are presented. In particular, our continuous deformation mode simulations almost perfectly replicate the results from real-world experimental data and are in line with predictions using other MD force fields. Our thorough investigation of Kapton^® also includes an analysis of the anisotropy of normal stresses, as well as the effect of simulation properties on the predicted Young’s moduli. Furthermore, the polyimide pyromellitic dianhydride/2-(4-aminophenyl)-1H-benzimidazole-5-amine (PMDA-BIA) was investigated to draw a more thorough picture of the usability of the OPLS-AA force field for polyimides. Full article

In this work, we aim to understand and predict the thermal properties of automotive lubricants using non-equilibrium molecular dynamics. After a previous study on model materials for the mechanical parts of a car engine, we now focus on the thermal conductivity $\kappa$ of the poly-$\alpha$-olefin base oil (PAO4) using the well-known sink and source method to study the response of the system to an imposed heat flux. We present a detailed methodology for the calculation of $\kappa$, taking into account specific constraints related to the system under study, such as large steady-state fluctuations and rapidly growing stationarization times. We provide thermal conductivity results using four different force fields, including OPLS-AA, PCFF and COMPASS, in a temperature range of 300 to 500 K, which corresponds to the typical operating range of a car engine. The results are compared to experimental measurements performed on the commercial compound using the laser flash method. Agreement at room temperature is shown to be excellent for our in-house force field. Full article

Polychlorinated dibenzo-p-dioxins (PCDD) are persistent organic pollutants which result as byproducts in industrial or combustion processes and induce toxicity in both wildlife and humans. In this study, all seven PCDD, tetrachlorinated dibenzo-p-dioxins (TCDD), pentachlorinated dibenzo-p-dioxins (P5CDD), hexachlorinated dibenzo-p-dioxins (H6CDD), heptachlorinated dibenzo-p-dioxins (H7CDD), and octachlorinated dibenzo-p-dioxins (OCDD) were studied in interaction with two cyclodextrins, β-CD and γ-CD, resulting in a total of 40 host–guest complexes. The flexibility of the cyclodextrins was given by the number of glucose units, and the placement of the chlorine groups on the dioxins structure accounted for the different complex formed. Various geometries of interaction obtained by guided docking were studied, and the complexation and binding energy were calculated in the frame of MM+ and OPLS force fields. The results show that the recognition of the PCDD pollutants by the CD may be possible through the formation of PCDD:CD inclusion complexes. This recognition is based on the formation of Coulombic interactions between the chlorine atom of the PCDD and the primary and secondary hydroxyl groups of the CD and van der Waals interaction of the CD hydrophobic cavity with PCDD aromatic structures. Both MM+ and OPLS calculus resulted in close values for the complexation and binding energies. Molecular mechanics calculations offer a proper insight into the molecular recognition process between the PCDD compounds and CD molecules, proved by a good description of the C-H···O bonds formed between the guest and host molecules. It was shown for the first time that CD may efficiently trap PCCDs, opening the way for their tremendous potential use in environmental remediation. Full article

Thermal conductivities of polybutadiene crosslinked with sulfur as a function of the heat flux autocorrelation function by using an equilibrium molecular dynamic (EMD) simulation were investigated. The Green–Kubo method was used to calculate thermal conductivities. All simulations were performed by applying the LAMMPS software (version 3 Mar 2020) package. The united-atom force field (OPLS-UA) from the Moltemplate software (version 2.20.3) was applied in the simulations. The influence of uniform and random distributions of sulfur in polybutadiene on the final value of thermal conductivities was studied by polymeric model structures with similar and variable degrees of crosslinking. The results showed that for identical degrees of crosslinking, the distribution of crosslinkers in the polymeric model structures significantly influenced the final value of thermal conductivity. Moreover, the influence of the crosslinking degree on the final value of thermal conductivity was studied by considering polymeric model structures with different degrees of crosslinking. The results demonstrate that by having a random distribution of sulfur, the thermal conductivity will be enhanced. However, by increasing the degree of crosslinking to the higher percentage in random crosslinked model structures, the value of thermal conductivity drops significantly due to possible higher crystallization of the model structures, which decrease the degree of freedom for phonon contributions. Full article

Molecular dynamics simulations employing the all-atom optimized potential for liquid simulations (OPLS-AA) force field were performed for determining self-diffusion coefficients ($D_{11}$) of ethanol and tracer diffusion coefficients ($D_{12}$) of solutes in ethanol at several temperature and pressure conditions. For simulations employing the original OPLS-AA diameter of ethanol’s oxygen atom (${\sigma }_{\mathrm{OH}}$), calculated and experimental diffusivities of protic solutes differed by more than 25%. To correct this behavior, the ${\sigma }_{\mathrm{OH}}$ was reoptimized using the experimental $D_{12}$ of quercetin and of gallic acid in liquid ethanol as benchmarks. A substantial improvement of the calculated diffusivities was found by changing ${\sigma }_{\mathrm{OH}}$ from its original value (0.312 nm) to 0.306 nm, with average absolute relative deviations (AARD) of 3.71% and 4.59% for quercetin and gallic acid, respectively. The new ${\sigma }_{\mathrm{OH}}$ value was further tested by computing $D_{12}$ of ibuprofen and butan-1-ol in liquid ethanol with AARDs of 1.55% and 4.81%, respectively. A significant improvement was also obtained for the $D_{11}$ of ethanol with AARD = 3.51%. It was also demonstrated that in the case of diffusion coefficients of non-polar solutes in ethanol, the original ${\sigma }_{\mathrm{OH}}=0.312$ nm should be used for better agreement with experiment. If equilibrium properties such as enthalpy of vaporization and density are estimated, the original diameter should be once again adopted. Full article

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1–C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand’s reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich–Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C₂₇H₂₃Cl₂CoFN₅O₃ exhibited profound anti-proliferative activity against the EAC cell line with a significant IC₅₀ value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF₁₆₅, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated. Full article

Polyisoprene, with a high degree of polymerization, is the main component of natural rubber. In the industrial production process, it is necessary to adjust the length of the macromolecule of polyisoprene to improve its plasticity. It is thus of vital importance to explore the effect of the degree of polymerization of polyisoprene on its properties, e.g., mechanical property and thermal property. Molecular dynamics simulations link microstructure to macroscopic properties. In this paper, Moltemplate was used to establish polyisoprene models with different degrees of polymerization, and the mechanical properties of polyisoprene under uniaxial tension were analyzed under an OPLS all-atom force field. The results showed that the strength and elastic modulus of the material increased with the increase in the degree of polymerization of the molecular chain. In the process of tensile loading, the non-bonded potential energy played a dominant role in the change of the total system potential energy. Then, the thermal conductivity of polyisoprene with different degrees of polymerization was calculated by the non-equilibrium molecular dynamics method (NEMD). The thermal conductivity of PI was predicted to converge to 0.179 W/(m·K). The mechanism of thermal conductivity of the polymer containing branched chains was also discussed and analyzed. The research content of this paper aims to provide theoretical support for improving the mechanical and thermal properties of natural rubber base materials. Full article

The increasing interest in the molecular mechanism of the binding of different agonists and antagonists to $\mathsf{\beta }$₂-adrenergic receptor ($\mathsf{\beta }$₂AR) inactive and active states has led us to investigate protein–ligand interactions using molecular docking calculations. To perform this study, the 3.2 Å X-ray crystal structure of the active conformation of human $\mathsf{\beta }$₂AR in the complex with the endogenous agonist adrenaline has been used as a template for investigating the binding of two exogenous catecholamines to this adrenergic receptor. Here, we show the derivation of L-DOPA and Droxidopa OPLS all atom (AA) force field (FF) parameters via quantum mechanical (QM) calculations, molecular dynamics (MD) simulations in aqueous solutions of the two catecholamines and the molecular docking of both ligands into rigid and flexible $\mathsf{\beta }$₂AR models. We observe that both ligands share with adrenaline similar experimentally observed binding anchor sites, which are constituted by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. Moreover, both L-DOPA and Droxidopa molecules exhibit binding affinities comparable to that predicted for adrenaline, which is in good agreement with previous experimental and computational results. L-DOPA and Droxidopa OPLS AA FFs have also been tested by performing MD simulations of these ligands docked into $\mathsf{\beta }$₂AR proteins embedded in lipid membranes. Both hydrogen bonds and hydrophobic interaction networks observed over the 1 $\mathsf{\mu }$s MD simulation are comparable with those derived from molecular docking calculations and MD simulations performed with the CHARMM FF. Full article

Our work concerns the study of four candidate drug compounds of the terpenoid family, found as essential oil ingredients in species of the Greek endemic flora, namely carvacrol, p-cymene, γ-terpinene, and thymol, via the simulation method of molecular dynamics. Aquatic solutions of each compound, as well as a solution of all four together in realistic (experimental) proportions, are simulated at atmospheric pressure and 37 °C using an OPLS force field combined with TIP3P water. As verified, all four compounds exhibit a strong tendency to phase-separate, thereby calling for the use of carrier molecules as aids for the drug to circulate in the blood and enter the cells. Systems of two such carrier molecules, the hyperbranched poly(ethylene imine) (HBPEI) polyelectrolyte and hyperbranched polyglycerol (HPG), are examined in mixtures with carvacrol, the most abundant among the four compounds, at a range of concentrations, as well as with all four compounds present in natural proportions. Although a tendency of the terpenoids to cluster separately persists at high concentrations, promising association effects are observed for all drug–polymer ratios. HBPEI systems tend to form diffuse structures comprising small mixed clusters as well as freely floating polymer and essential oil molecules, a finding attributed to the polymer–polymer electrostatic repulsions, which here are only partially screened by the counterions. On the other hand, the electrically neutral HPG molecules cluster together with essential oil species to form a single nanodroplet. Currently, terpenoid–polymer clusters near lipid bilayer membranes are being studied to determine the propensity of the formed complexes to enter cell membranes. Full article

Self-assembled cyclic peptide nanotubes with alternating D- and L-amino acid residues in the sequence of each subunit have attracted a great deal of attention due to their potential for new nanotechnology and biomedical applications, mainly in the field of antimicrobial peptides. Molecular dynamics simulations can be used to characterize these systems with atomic resolution at different time scales, providing information that is difficult to obtain via wet lab experiments. However, the performance of classical force fields typically employed in the simulation of biomolecules has not yet been extensively tested with this kind of highly constrained peptide. Four different classical force fields (AMBER, CHARMM, OPLS, and GROMOS), using a nanotube formed by eight D,L-α-cyclic peptides inserted into a lipid bilayer as a model system, were employed here to fill this gap. Significant differences in the pseudo-cylindrical cavities formed by the nanotubes were observed, the most important being the diameter of the nanopores, the number and location of confined water molecules, and the density distribution of the solvent molecules. Furthermore, several modifications were performed on GROMOS54a7, aiming to explore acceleration strategies of the MD simulations. The hydrogen mass repartitioning (HMR) and hydrogen isotope exchange (HIE) methods were tested to slow down the fastest degrees of freedom. These approaches allowed a significant increase in the time step employed in the equation of the motion integration algorithm, from 2 fs up to 5–7 fs, with no serious changes in the structural and dynamical properties of the nanopores. Subtle differences with respect to the simulations with the unmodified force fields were observed in the concerted movements of the cyclic peptides, as well as in the lifetime of several H-bonds. All together, these results are expected to contribute to better understanding of the behavior of self-assembled cyclic peptide nanotubes, as well as to support the methods tested to speed up general MD simulations; additionally, they do provide a number of quantitative descriptors that are expected to be used as a reference to design new experiments intended to validate and complement computational studies of antimicrobial cyclic peptides. Full article

Polyethylene vanillic (PEV), a bio-based material, has mechanical and thermal properties similar to polyethylene terephthalate (PET), the most common polymer used in industries. The present study aimed to investigate and compare their structural dynamics and physical data using a computational approach. The simple model of a single-chain polymer containing 100 repeating units was performed by all-atom molecular dynamics (MD) simulations with refined OPLS–AA force field parameters. As a result, the flexibility of the PEV structure was greater than that of PET. PET and PEV polymers had the predicted glass transition temperature T_g values of approximately 345 K and 353 K, respectively. PEV showed a slightly higher T_g than PET, consistent with current experimental evidence. Full article

Electrostatic interactions have a determining role in the conformational and dynamic behavior of polyelectrolyte molecules. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in a water solution with the most commonly used K⁺ or Na⁺ counterions, were investigated using atomistic molecular dynamics (MD) simulations. We performed a comparison of seven popular force fields, namely AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and using two common corrections for overbinding of ions, the non-bonded fix (NBFIX), and electronic continuum corrections (ECC). These corrections were originally introduced to correct for the often-reported problem concerning the overbinding of ions to the charged groups of polyelectrolytes. In this work, a comparison of the simulation results with existing experimental data revealed several differences between the investigated force fields. The data from these simulations and comparisons with previous experimental data were then used to determine the limitations and strengths of these force fields in the context of the structural and dynamic properties of anionic polyamino acids. Physical properties, such as molecular sizes, local structure, and dynamics, were studied using two types of common counterions, namely potassium and sodium. The results show that, in some cases, both the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of the ions and charged side chain groups. The local structures and dynamics are more sensitive to dihedral angle parameterization, resulting in a preference for defined monomer conformations and the type of correction used. We also provide recommendations based on the results. Full article

Dimerization free energies are fundamental quantities that describe the strength of interaction of different molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely difficult, due to the size of the systems and the small energy differences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings, and compared three models from popular online servers for atomistic force fields, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force field, the profiles for the dimerization free energy of these compounds are very similar. However, significant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecules, resulting in force field dependent preferred stacking modes; for example, in the cases of pyrene and tetracene. Our results provide a useful background study for using topology builders to model systems which rely on stacking of aromatic moieties, and are relevant in areas ranging from drug design to supramolecular assembly. Full article

Poly(ethylene oxide) (PEO)-based polymers are common hosts in solid polymer electrolytes (SPEs) for high-power energy devices. Molecular simulations have provided valuable molecular insights into structures and ion transport mechanisms of PEO-based SPEs. The calculation of thermodynamic and kinetic properties rely crucially on the dependability of the molecular force fields describing inter- and intra-molecular interactions with the target system. In this work, we reparametrized atomic partial charges for the widely applied optimized potentials for liquid simulations (OPLS) force field of PEO. The revised OPLS force field, OPLS^R, improves the calculations of density, thermal expansion coefficient, and the phase transition of the PEO system. In particular, OPLS^R greatly enhances the accuracy of the calculated dielectric constant of PEO, which is critical for simulating polymer electrolytes. The reparameterization method was further applied to SPE system of PEO/LiTFSI with O:Li ratio of 16:1. Based on the reparametrized partial charges, we applied separate charge-scaling factors for PEO and Li salts. The charge-rescaled OPLS^R model significantly improves the resulting kinetics of Li⁺ transport while maintaining the accurate description of coordination structures within PEO-based SPE. The proposed OPLS^R force field can benefit the future simulation studies of SPE systems. Full article