Molecular Structural Model Research Articles

Construction and Evaluation of a Medium-Rank Coal Molecular Model Using a Hybrid Experimental–Simulation–Theoretical Method

To aid the in-depth understanding of the coal structure and its mechanism of reactivity and adsorption in medium-rank coal, a plausible molecular structural model for TunLan no.2 coal in China was ...

(Invited) Molecular Scale Modeling of Structure, Transport and Electrochemistry of Aqueous and Non-Aqueous Electrolytes

A molecular scale insight into ion transport and decomposition is important for understanding deficiencies of the currently used aqueous and non-aqueous electrolytes. In this presentation I will summarize progress made towards improving molecular scale understanding of the structure and electrochemistry for a wide range of aqueous and non-aqueous electrolytes. Because no one simulation technique is capable of efficiently capturing all transport and electrochemical properties at interfaces, we will utilize a combination of multiple modeling methods: a) density functional theory (DFT) studies of the solvent reactions on cathode surfaces and at the solid electrolyte interphase (SEI) covering lithium metal; b) representative quantum chemistry (QC) calculations performed on the representative small model electrolyte clusters to estimate oxidation and reduction; c) molecular dynamics (MD) using APPLE&P polarizable force field to examine bulk and interfacial properties of electrolytes and electrochemical interfaces; d) new generation of the force fields for accurately capturing electrolyte transport properties and transference number. Combined together information from these modeling scales suggests numerous strategies for stabilizing the electrolyte – electrode interfaces for numerous aggressive high energy density cathodes combined coupled with graphite and metal anodes.

Inclusion of tributyrin during enzymatic synthesis of cyclodextrins by β-cyclodextrin glycosyltransferase from Bacillus circulans

Tributyrin is a precursor of butyric acid, which is beneficial to intestinal health. Due to its unpleasant odor and poor solubility, tributyrin is usually used after inclusion complexation with suitable wall materials. In this paper, tributyrin was creatively added to the enzymatic synthesis of cyclodextrins catalyzed by β-cyclodextrin glycosyltransferase from Bacillus circulans STB01. The tributyrin formed inclusion complexes directly during enzymatic cyclodextrins synthesis and increased the yield of cyclodextrins from 25.84% to 44.01%. This process was investigated by determining inclusion complex stability constant and by using molecular modeling and 1H NMR. The inclusion complexes stability constants of tributyrin with α-, β-, and γ-cyclodextrin were 25.11, 58.56 and 6.93 L/mol, respectively. β-Cyclodextrin had the largest stability constant and the most significant increase in yield (72.80%). Molecular modeling of the three-dimensional structures of the tributyrin-cyclodextrin inclusion complexes indicated that the morphology of the complexed groups was related to the size of the cyclodextrin cavity. Finally, the supramolecular structures were verified with 1H NMR through the chemical shift changes of protons at key positions. This study created a new method and a new inclusion wall material, instead of single pure cyclodextrin for complexing guest molecules. These advances are important because they may expand the application of cyclodextrins due to significant cost reduction.

Advanced molecular structural mechanics model for carbon nanotubes incorporating the 2nd generation REBO potential

Molecular mechanics models like the molecular structural mechanics (MSM) model have been proven to be a valuable tool for the investigation of carbon nanotubes. This class of models is based on a chemical force field representing the bonds present in the structure. Up to now, the underlying chemical force field applied in the MSM model is usually based on harmonic potentials. This simple approach comes with major drawbacks limiting the abilities of the MSM approach. In order to overcome these limitations, the present work integrates the 2nd generation reactive bond order potential (REBO), which is a sophisticated chemical force field, into the MSM approach. The development of this advanced MSM model is given in detail. As a demonstration of its capabilities, the elastic properties of different armchair and zig-zag CNTs are investigated numerically. It was found, that the results for the elastic properties differ significantly with the choice of the underlying chemical force field. The arising differences are discussed and reasons for the occurring behavior are given. The developed advanced MSM approach on the basis of the REBO potential strongly enhances the capabilities of the MSM approach while maintaining its excellent accessibility and applicability together with a low computational effort.

Molecular design and virtual docking of oligopeptides for binding and elimination interleukin-6 from blood plasma

Binding of interleukin-6 (IL-6) is the perspective target for the anti-inflammatory therapy in many pathological conditions (sepsis, autoimmune pathology, allergic diseases). The aim of this work was to develop and study the binding IL-6 oligopeptides. To achieve the goal, were set and successfully solved the following tasks: studying three-dimensional models of molecular structures of IL-6 incombination with the R-IL-6 and gp130, prediction and virtual synthesis low molecular weight oligopeptides; evaluating the free energy of IL-6 binding for identity the most effective oligopeptide; studying the changing the concentration of IL-6 inthe model solution after contact with experimental oligopeptides. In the article presents the binding IL-6 energy of 62 peptides, designed using the PyMol. Energy was calculated in the Chimera program using the AutodockVina application. There are also presented results of in vitro experiments interacting 7 sextapeptides, 2 tetrapeptides, and 3 tripeptides with recombinant IL-6. The effectiveness of the peptides was calculated by reducing the concentration of cytokine in solution as a percentage of the initial concentration.The free binding energy has shown that the efficiency of binding increases with an increase in the total number of amino acids and, in particular, of aromatic amino acids in the oligopeptide. Correlation analysis showed that the molecular modeling method is not absolutely effective for predicting the structure of an oligopeptide, however, it can be used as one of the preliminary steps for analyzing the interaction between molecules and studying the optimal interaction points. Two oligopeptides were identified as the most promising for further synthesis as the ligands for binding and evaluating IL-6 inhuman blood plasma.

Structural Elucidation, 3D Molecular Modeling and Antibacterial Activity of Ni (II), Co (II), Cu (II) and Mn (II) Complexes Containing Salophen Ligand

The salophen ligand and its complexes of Ni(II), Co(II), Cu(II), and Mn(II) are explored in terms of synthesis, conductivity; magnetic measurements, elemental analysis, FT-IR; electronic spectra, and antibacterial activities. The 3D molecular modeling structures of the ligand and its metal complexes are obtained by using Argus lab software. The experimental data shows that the ligand is tetradentate and bonded to the metal ion via N2O2 donor atoms. Antibacterial activity of the synthesized compounds are checked against the microbes Bacillus cereus and Escherichia coli. The metal complexes exhibit antibacterial activity higher than that of the free ligand. This works contributes to the science of Schiff base compounds, in addition to stimulating the synthesis of new ligands and its complexes for the future advancement of coordination chemistry.

High Glass‐Transition Temperature Polymer Networks Harnessing the Dynamic Ring Opening of Pinacol Boronates

AbstractDifferential scanning calorimetry of high molar mass poly(4‐vinylphenylboronic acid, pinacol ester)s evidenced unusual reactive events above 120 °C, resulting in a high glass‐transition temperature of 220 °C. A reversible ring‐opening reactivity of pinacol boronates is proposed, involving a nucleophilic attack on the sp2 boron and subsequent bridging between boron atoms by interconnected pinacol moieties to form a densely crosslinked network with high Tg. FTIR, solid‐state NMR investigations, and rheology studies on the polymer as well as double‐tagging analyses on molecular model structures and theoretical calculations further support this hypothesis and indicate a ring‐opening inducing crosslinking. When diluted in an apolar solvent such as toluene, the polymer network can be resolubilized via ring closing, thus recovering the entropically favored linear chains featuring cyclic boronate esters.

High Glass-Transition Temperature Polymer Networks Harnessing the Dynamic Ring Opening of Pinacol Boronates.

Differential scanning calorimetry of high molar mass poly(4-vinylphenylboronic acid, pinacol ester)s evidenced unusual reactive events above 120 °C, resulting in a high glass-transition temperature of 220 °C. A reversible ring-opening reactivity of pinacol boronates is proposed, involving a nucleophilic attack on the sp2 boron and subsequent bridging between boron atoms by interconnected pinacol moieties to form a densely crosslinked network with high Tg . FTIR, solid-state NMR investigations, and rheology studies on the polymer as well as double-tagging analyses on molecular model structures and theoretical calculations further support this hypothesis and indicate a ring-opening inducing crosslinking. When diluted in an apolar solvent such as toluene, the polymer network can be resolubilized via ring closing, thus recovering the entropically favored linear chains featuring cyclic boronate esters.

A2-Net: Molecular Structure Estimation from Cryo-EM Density Volumes

Constructing of molecular structural models from CryoElectron Microscopy (Cryo-EM) density volumes is the critical last step of structure determination by Cryo-EM technologies. Methods have evolved from manual construction by structural biologists to perform 6D translation-rotation searching, which is extremely compute-intensive. In this paper, we propose a learning-based method and formulate this problem as a vision-inspired 3D detection and pose estimation task. We develop a deep learning framework for amino acid determination in a 3D Cryo-EM density volume. We also design a sequence-guided Monte Carlo Tree Search (MCTS) to thread over the candidate amino acids to form the molecular structure. This framework achieves 91% coverage on our newly proposed dataset and takes only a few minutes for a typical structure with a thousand amino acids. Our method is hundreds of times faster and several times more accurate than existing automated solutions without any human intervention.

Molecular Modeling of Structure and Dynamics of Nafion Protonation States.

We present the results of the atomistic molecular dynamics modeling of different protonation states of Nafion at varying hydration levels. Previous experiments have shown that the degree of deprotonation (DDP) of the sulfonic acid groups in a Nafion membrane varies significantly upon hydration. Our goal is to provide insights into the effects of variable protonation states and water content on the internal structure and vehicular transport inside the Nafion membrane. The Nafion side chain lengths showed a weak increasing trend with increasing DDP at all hydration levels, exposing more of the sulfonic acid groups to the hydrophilic/water phase. The water-phase characteristic size/diameter decreased with increasing DDP, but, interestingly, the average number of water molecules per cluster increased. The probability of water–hydronium hydrogen bond formation decreased with increasing DDP, despite an increase in the total number of such hydrogen bonds. The water diffusion was largely unaffected by the state of deprotonation. In contrast to that, the hydronium ion diffusion slowed down with increasing DDP in the overall membrane. The hydronium ion residence times around the sulfonic acid group increased with increasing DDP. Our simulations show a strong connection between the morphology of the water domains and protonation states of Nafion. Such a connection can also be expected in polyelectrolyte membranes similar to Nafion.

Molecular modeling and computational study of the chiral-dependent structures and properties of self-assembling diphenylalanine peptide nanotubes.

The structure and properties of diphenylalanine (FF) peptide nanotubes (PNT) based on phenylalanine were investigated by various molecular modeling methods. The main approach employed semi-empirical quantum-chemical methods (PM3 and AM1). Ab initio, density functional theory methods and molecular mechanical approaches were also used. Both model structures and structures extracted from experimental crystallographic databases obtained by X-ray methods were examined. A comparison of optimized model structures and structures obtained by natural self-assembly revealed important differences depending on chirality: D and L. In both the cases, the effect of chirality on the results of self-assembly of FF PNT was established: PNT based on the D-FF has large condensation energy E0 in the transverse direction, and form thicker and shorter PNT bundles than those based on L-FF. A topological difference was established: model PNT were optimized into structures consisting of rings, while naturally self-assembled PNT consisted of helical turns. The latter nanotubes differed from the original L-FF and D-FF and formed helix structures of different chirality signs in accordance with the alternation rule of chirality due to macromolecule hierarchy. A topological transition between ring and helix turn PNT structures is discussed: self-assembled natural helix structures are favorable and their energy is lower by a value of the order of one to several eV.

Thermal environment and strain energy related micro-model for properties of carbon nanotubes

In this paper, a molecular structural mechanics model is proposed to study the effect of thermal environment on elastic properties of carbon nanotubes. The covalent bonds are traded as a truss in this new model. The influence of the temperature on Young’s modulus and shear modulus of both armchair and zigzag carbon nanotubes are investigated. According to the principle of elastic theory, a temperature-dependent continuum shell model of strain energy density is also established. The strain energy density of single-walled carbon nanotubes (SWCNTs) decreases with the increase of temperature. The Young's modulus of SWCNTs increases with the increase of tube diameter, but decreases with the increase of temperature. The temperature-dependent modulus of SWCNTs has a similar trend of change with multi-walled carbon nanotubes (MWCNTs), but MWCNTs are more sensitive to the wall thickness.

Spectroscopic characterization of non-covalent CuPc-GO system. Experiment and theory

In this study we report on UV-vis, IR and Raman studies of non-covalent copper phthalocyanine (CuPc) – flake graphene oxide (GO) complex in water and in the solid phase. Experimental results were supported by molecular modeling of structure, electronic and vibrational parameters for free CuPc and its 1 : 1 complexes with water, benzene, phenol, neutral and deprotonated benzoic acid. HOMO-LUMO gaps for these complexes were calculated and compared with data derived from the absorption edge of Q-band in the recorded UV-vis spectra for free CuPc and its adduct with GO in water. Small but non-negligible changes in position of spectral bands observed as result of CuPc interaction with GO were consistent with theoretical models predicted by density functional theory (DFT). Both the observed spectroscopic changes and theoretical shifts of spectral bands supported a direct interaction between CuPc and GO. The interaction site of CuPc was copper ion - small molecules were bound preferably to Cu2+ and its vicinity as an additional axial ligand forming a kind of T-shaped structure. In case of benzene and phenol sandwich type complexes were formed.

Mutational analysis of 3 Glanzmann′s thrombasthenia pedigrees

Objective To explore the molecular pathogenesis of 3 Glanzmann′s thrombasthenia pedigree by using bioinformatics software and provide evidence for in vitro experiments. Methods The genetic analysis of 3 pedigree diagnosed as Glanzmann′s thrombasthenia was carried out. Clustalx-2.1 win software was used to analyze the conservatism of mutant sites in homologous sequences. Bioinformatics software such as PolyPhen-2, PROVEAN, SIFT and Mutationtaster was used to analyze the biological effect of mutation. SPDBV software constructed the molecular structure model of mutant protein and evaluated the influence of mutation on protein structure. Results The found in 3 Glanzmann′s thrombasthenia pedigree were ITGA2B: c. 814G>C (p. Val272Leu), ITGA2B: c. 432G>A (p. Trp144Ter) and ACTN1: c. 2458A>G (p. Ile820Val). All three mutations were highly conserved among homologous species. Mutationtaster software showed that 3 new mutations were likely pathogenic. PolyPhen-2 and PROVEAN software showed ITGA2B p.Val272Leu and ACTN1 p.Ile820Val were benign and SIFT software showed that ITGA2B p. Val272Leu were likely pathogenic, while ACTN1 p. Ile820Val is benign. The result of SPDBV software showed that the Val272 of ITGA2B was transformed to Leu, neutralizing all the original hydrogen bond. The Trp144 of ITGA2B is transformed to Ter, resulting in the truncated proteins with only 113 amino acid residues. All these mutations affected the molecular structure of GPⅡb, resulting in a decrease ofGPⅡb/Ⅲa expression. When the Ile820 of ACTN1 is transformed to Val, onlyretained the hydrogen bond of Ile820 and Asp822, neutralized the rest hydrogen bond, whichaffected the molecular structure and protein function of ACTN1. Conclusion The mutations of ITGA2B:c.814G>C (p.VAL272LEU), ITGA2B:c.432G>A (p.Trp144Ter) and ACTN1:c.2458A>G (p.Ile820Val) are pathogenic. Key words: Thrombasthenia; Pedigree; Integrin alpha2; Integrin beta3; Actinin; Mutation

Characterization of gas-phase thorium nitride.

Properties of gas-phase thorium nitride, ThN, have been experimentally determined from a combined optical and microwave spectroscopic study. An intense band near 555 nm has been assigned as the [18.0]1.5-X2Σ+ (0,0) transition and recorded at high resolution in the presence of static electric and magnetic fields. The observed optical Stark shifts were analyzed to determine permanent electric dipole moments, μ→el for the [18.0]1.5 and X2Σ+ states of 4.38 ± 0.02D and 5.11 ± 0.09D, respectively. Zeeman shifts were used to determine the magnetic g-factors. The pure rotational spectrum was recorded using a separated field optical pump/probe microwave repopulation scheme and analyzed to determine the bond length and 14N magnetic hyperfine and nuclear electric quadrupole parameters. A molecular orbital correlation diagram and ligand field electronic structure models are used to provide a qualitative interpretation of the electronic state ordering, magneto- and electro-static properties, and hyperfine interactions. Electronic structure calculations for the X2Σ+ state were performed, and results were compared with observations. Observed trends in μ→el for the ThX (X = N, S, O, F, and Cl) series are discussed.

Purification and biochemical characterization of FrsA protein from Vibrio vulnificus as an esterase.

Fermentation-respiration switch protein (FrsA) was thought to play an important role in controlling the metabolic flux between respiration and fermentation pathways, whereas the biochemical function of FrsA was unclear yet. A gene coding for FrsA protein from Vibrio vulnificus was chemically synthesized. The recombinant VvFrsA was expressed as a soluble protein and purified by Ni-NTA affinity chromatography. The protein had a subunit molecular weight of ca. 45 kDa by SDS-PAGE and preferred short-chain esters when p-nitrophenyl alkanoate esters were used as substrates. Optimum condition for VvFrsA was found to be at pH 9.0 and 50 °C. The protein retained high esterase activity at alkaline condition and would denature slowly at over 50 °C. With p-nitrophenyl acetate as the substrate, the Km and kcat were determined to be 18.6 mM and 0.67 s-1, respectively, by steady-state kinetic assay. Molecular dynamics simulation and docking model structure revealed that p-nitrophenyl acetate could be the substrate of VvFrsA. In conclusion our results demonstrated that the protein was able to catalyze the hydrolysis of esters, especially p-nitrophenyl acetate, for the first time.

Raman spectroscopic study of nonlinear modulation on Fermi resonance of acetonitrile by hydrogen-bonding network

Raman spectra of acetonitrile-water mixtures are measured in different acetonitrile concentration fractions. The nitrile stretch (v2) and the combination (v3 + v4) modes are coupled by Fermi resonance. We extract the Fermi resonance parameters and find that the frequency separation shows non-linear dependence as a function of acetonitrile concentration fractions. v2 ~ v3 + v4 Fermi doublets intensity ratio exhibits nonlinearity, which is accelerated with the decreasing of the Fermi coupling strength. The OH stretching region is also investigated in order to reveal the variation of the water structure. Our data show that there are strong relationships between the intensity of ~3225 cm−1 band and the v2~v3 + v4 Fermi resonance. Because the nitrile stretch and Fermi resonance are very environmental sensitive, the nonlinear modulation on Fermi resonance and the non-regular intensity ratio are attributed to the change of water hydrogen-bonding network. The results provide useful structural and spectral insights for the design of new experiments and the molecular structure modeling.

Structure Modelling of CaV1.1 Reveals Functional Trans-Domain Interactions Involved in Voltage Sensing

Voltage-gated calcium channels (CaV) consist of four homologous but non-identical repeats (I, II, III, IV), each containing a separate voltage-sensing domain (VSD) arranged around the common channel pore. Within each VSD the positive gating charges (R1, R2, R3, R4) in the transmembrane helix S4 sequentially interact with negative counter-charges in helices S2 and S3 to support the movement of the gating charges across the electrical field of the membrane and thus to activate or deactivate the channel. Previously we identified an interaction between R1 and R2 with aspartate 1196 (D4) in S3 of the VSD-IV of CaV1.1 that is critical for modulation of voltage-sensitivity and current-density by alternative splicing in the IVS3-S4 linker. Using molecular structure modeling we now identified an additional interaction with a glutamate (E216) in S5 of VSD-I that participates in the R1/R2-D4 interaction of VSD-IV. Charge-neutralization (E216Q) or substitution with alanine (E216A) in CaV1.1e caused a 7mV and 16mV, respectively, right-shift of voltage-dependence of activation and a 30 % reduction in current density. This effect is specific to the splice variant lacking exon 29 and is quantitatively in the same range as previously observed when R1, R2, or D4 were mutated; indicating that this trans-domain interaction between repeats I and IV participates in the voltage-dependent gating and its modulation by alternative splicing. Structure models of CaV1.1 in the activated and pre-open state show that the four VSD differ greatly regarding their intra-domain interactions, consistent with their specific contributions to CaV1.1 gating properties. The newly discovered inter-domain interaction is unique for VSD-I and IV. Together in silico structure modelling of this pseudo-tetrameric ion channel revealed hitherto not appreciated differences between the VSDs and a functional inter-domain interaction. Support: Austrian Science Fund (FWF) grant P30402.

Electromechanical vibration of microtubules and its application in biosensors.

An electric field (EF) has the potential to excite the vibration of polarized microtubules (MTs) and thus enable their use as a biosensor for the biophysical properties of MTs or cells. To facilitate the development, this paper aims to capture the EF-induced vibration modes and the associated frequency for MTs. The analyses were carried out based on a molecular structural mechanics model accounting for the structural details of MTs. Transverse vibration, radial breathing vibration and axial vibration were achieved for MTs subject to a transverse or an axial EF. The frequency shift and stiffness alteration of MTs were also examined due to the possible changes of the tubulin interactions in physiological or pathological processes. The strong correlation achieved between the tubulin interaction and MT vibration excited by EF provides a new avenue to a non-contacting technique for the structural or property changes in MTs, where frequency shift is used as a biomarker. This technique can be used for individual MTs and is possible for those in cells when the cytosol damping on MT vibrations is largely reduced by the unique features of MT-cytosol interface.

Modeling of molecular and properties of anthracite base on structural accuracy identification methods

Molecular model construction is essential for the study of the energy conversion process, the combustion reaction mechanism and the clean utilization of coal. In this study, an anthracite molecular structure of GBW(E)110031 was constructed based on the structural accuracy identification methods, such as 13C nuclear magnetic resonance spectroscopy (13C NMR), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and quantitative chemical analysis. The 13C NMR spectrum was registered to analyze the carbon skeleton structure of the anthracite and twelve characteristic parameters of coal structures. The aromaticity, hydrogen aromaticity, and average aromatic nuclear size of the anthracite were calculated. These data were utilized to construct 17 basic structural units of aromatic carbon. The vibration modes of the carbon skeleton, several association forms of oxygen, and different types of functional group were confirmed based on the ATR-FTIR collected spectra. The content of functional groups and unsaturated aliphatic carbon alkenyl were determined by the calcium ion exchange method, the pyridine hydroxylamine hydrochloride oximation method and the bromine addition method. Based on these experimental data, a C202H104O21N2S2 anthracite molecular structure model was constructed. In the molecular structure model, benzene and naphthalene structures accounted for 70% of the mass of aromatic compounds, while aliphatic structures existed in the form of side chains and rings. Carbonyl group (CO) accounted for 85% of the oxygen atoms, while others existed in the form of carboxyl and hydroxyl groups. The nitrogen atoms presented in the structures of pyridine and pyrrole, and the sulfur atoms presented in the structures of thiophene. The theoretical analysis matched well with 13C NMR spectra interpretation, which was verified the reliability and rationality of the molecular structure model and analytical method.