Structure Of Trimers Research Articles

Carboxylated chitosan improved the stability of phycocyanin under acidified conditions

Phycocyanin, a natural blue colorant, derived from Spirulina platensis, is now widely used in the food industry. However, its main drawbacks are loss of color and denature of structure in an acidic environment. In this study, carboxylated chitosan (0.1 %–1 % w/v) was chosen as an additive in acid-denatured phycocyanin for preserving phycocyanin's blue color and natural structure. Zeta-potential and particle size revealed that the carboxylated chitosan with high negative charge adsorbed on phycocyanin and provided stronger electrostatic repulsion to overcome the protein aggregation. Ultraviolet-visible absorption spectrum and fluorescence spectroscopy showed that the carboxylated chitosan recovered the microenvironment of tetrapyrrole chromophores and β-subunits, which led the secondary structure changed and the trimers depolymerized into the monomers changed by the acidic environment. Furthermore, Fourier transform infrared spectroscopy revealed highly negatively charged carboxylated chitosan with the groups (NH2, COOH and OH) could restored the microenvironment of tetrapyrrole chromophores and β-subunits of phycocyanin, and interact with phycocyanin through hydrogen bonding, NH bonding, ionic bonding and van der Waals, which led to a change in secondary structure and depolymerization of trimers into monomers. Our study demonstrated the carboxylated chitosan played a beneficial role in recovering the structure of acid-denatured phycocyanin and its blue color.

Molecular area dependences of monolayers at the air/water interface

The quantum chemical approach and a thermodynamic model for amphiphilic monolayers are used to find the temperature dependence of the area per amphiphile molecule in a monolayer at the onset of liquid-expanded – liquid-condensed phase transition (A c ). Quantum chemical calculations within the semiempiric PM3 method for clusterization thermodynamics and structure of surfactant dimers and trimers are used, as well as for assessment of their molecular area in an aggregate. Calculations are done for seven amphiphile classes: saturated and ethoxylated alcohols, saturated and unsaturated carboxylic acids, α-hydroxylic acids, N -acyl-substituted alanine and dialkyl-substituted melamine that are well experimentally explored. Calculations reflect the experimental data and show that a temperature increase leads to decrease of A c for an amphiphile with a given alkyl chain length, and vice versa with a chain length increase at a fixed temperature the A c value grows. It was shown that as the temperature increases the increment of A c per methylene unit of the hydrocarbon chain becomes less significant. The average values of the slope reflecting the change of A c per 1 ​°C for saturated and ethoxylated alcohols, saturated, cis - and trans -unsaturated carboxylic acids, α-hydroxylic acids, N -acyl-substituted alanine and dialkyl-substituted melamine are 0.57, 1.32, 1.14, 1.26, 1.15, 0.66, 1.07 and 0.67 ​Å 2 /°С, respectively. These data are quite similar to the experimental values of − d A c d T for tetradecanoic acid, dipalmitoyl-phosphatidylcholine and dipalmitoyl phosphatididic acid. The proposed approach can be used as a predictive tool for amphiphiles lacking experimental data.

Development of a synthetic nanoparticle vaccine presenting the HIV-1 envelope glycoprotein

Two-component self-assembling virus-like particles (VLPs) are promising scaffolds for achieving high-density display of HIV-1 envelope (gp140) trimers, which can improve the induction of neutralising antibodies (NAbs). In this study gp140 was displayed on the surface of VLPs formed by the AP205 phage coat protein. The CAP256 SU gp140 antigen was selected as the patient who this virus was isolated from developed broadly neutralising antibodies (bNAbs) shortly after superinfection with this virus. The CAP256 SU envelope is also sensitive to several bNAbs and has shown enhanced reactivity for certain bNAb precursors. A fusion protein comprising the HIV-1 CAP256 SU gp140 and the SpyTag (ST) (gp140-ST) was produced in HEK293 cells, and trimers were purified to homogeneity using gel filtration. SpyCatcher (SC)-AP205 VLPs were produced in Escherichia coli and purified by ultracentrifugation. The gp140-ST trimers and the SC-AP205 VLPs were mixed in varying molar ratios to generate VLPs displaying the glycoprotein (AP205-gp140-ST particles). Dynamic light scattering, negative stain electron microscopy and 2D classification indicated that gp140-ST was successfully bound to the VLPs, although not all potential binding sites were occupied. The immunogenicity of the coupled VLPs was evaluated in a pilot study in rabbits. One group was injected four times with coupled VLPs, and the second group was primed with DNA vaccines expressing Env and a mosaic Gag, followed by modified vaccinia Ankara expressing the same antigens. The animals were then boosted twice with coupled VLPs. Encouragingly, gp140-ST displayed on SC-AP205 VLPs was an effective boost to heterologously primed rabbits, leading to induction of autologous Tier 2 neutralising antibodies in 2/5 rabbits. However, four inoculations of coupled VLPs alone failed to elicit any Tier 2 antibodies. These results demonstrate that the native-like structure of HIV-1 envelope trimers and selection of a geometrically-suitable nanoparticle scaffold to achieve a high-density display of the trimers are important considerations that could improve the effect of nanoparticle-displayed gp140.

2,7-substituted fluorenone-based liquid crystal trimers: twist-bend nematic phase induced by outer thioether linkage

ABSTRACT 2,7-Substituted fluorenone has a planar and slightly bent aromatic structure and is used as a building block for organic liquid crystals (LCs). Herein, we report for the first time the synthesis, phase-transition behaviour, and mesophase structure of fluorenone-incorporated LC trimers that exhibit an emerging helical twist-bend nematic (NTB) phase. The LC trimers possess a central 2,7-ether-substituted fluorenone and bilateral cyanobiphenyl groups linked via odd alkylene C n H2n spacers (n = 7 or 9) with either ether or thioether outer linkages; these are abbreviated CBOnOFlnOnOCB and CBSnOFlnOnSCB, respectively. The CBOnOFlnOnOCB trimers having only ether linkages display only the conventional nematic (N) phase, whereas the outer thioether-linked CBSnOFlnOnSCB trimers form an NTB phase below the temperature range of the N phase. Furthermore, the phase-transition behaviour of these fluorenone-based LC trimers is compared with that of the corresponding all-biphenyl-based motif trimer analogues, CBOnOBOnOCB and CBSnOBOnSCB.

Structure and Dynamics of HIV-1 ENV Trimers on Native Virions Engaged in Living T Cells

Structure and Dynamics of HIV-1 ENV Trimers on Native Virions Engaged in Living T Cells

Quantum trimer models and topological SU(3) spin liquids on the kagome lattice

We construct and study quantum trimer models and resonating SU(3)-singlet models on the kagome lattice, which generalize quantum dimer models and the Resonating Valence Bond wavefunctions to a trimer and SU(3) setting. We demonstrate that these models carry a Z_3 symmetry which originates in the structure of trimers and the SU(3) representation theory, and which becomes the only symmetry under renormalization. Based on this, we construct simple and exact parent Hamiltonians for the model which exhibit a topological 9-fold degenerate ground space. A combination of analytical reasoning and numerical analysis reveals that the quantum order ultimately displayed by the model depends on the relative weight assigned to different types of trimers -- it can display either Z_3 topological order or form a symmetry-broken trimer crystal, and in addition possesses a point with an enhanced U(1) symmetry and critical behavior. Our results accordingly hold for the SU(3) model, where the two natural choices for trimer weights give rise to either a topological spin liquid or a system with symmetry-broken order, respectively. Our work thus demonstrates the suitability of resonating trimer and SU(3)-singlet ansatzes to model SU(3) topological spin liquids on the kagome lattice.

Light‐Harvesting Supramolecular Polymers: Energy Transfer to Various Polyaromatic Acceptors

A supramolecular light‐harvesting antenna consisting of 3,6‐disubstituted phosphodiester‐linked phenanthrene trimers (donors) was doped with different charged and uncharged polyaromatic and heteroaromatic acceptor chromophores. Excitation of the phenanthrene moieties is followed by energy transfer to the acceptor molecules and radiative relaxation. The self‐assembled fiber structure of the phenanthrene trimers is not altered by the dopant, as verified by atomic force microscopy (AFM). Among several neutral and cationic acceptor chromophores, benzo(a)pyrene emerged as one of the highest fluorescence quantum yields, reaching 31 % at a chromophore/phenanthrene ratio of 12 mol‐%. The energy transfer is probably a combination of Förster resonance energy transfer (FRET) and a coherent energy transfer mechanism.

Structure and Dynamics of HIV-1 Env Trimers on Native Virions Engaged in Living T Cells

The HIV-1 envelope glycoprotein (Env) mediates viral entry into the host cell. Although the highly dynamic nature of Env intramolecular conformations has been shown with single molecule spectroscopy in vitro, the bona fide Env intra and intermolecular mechanics when engaged in live T cells remains unknown. We used two photon fast fluorescence lifetime imaging detection of single-molecule Forster Resonance Energy Transfer occurring between fluorescent labels on HIV-1 Env. Our observations of Env dynamics reveal transitions between four intramolecular conformations of Env trimer and two additional intermolecular conformations that mediate Env clustering. Furthermore, we show that three broadly neutralizing anti-Env antibodies directed to different epitopes destabilise Env intermolecular dynamics and their clusters engaged to living T cells. Thus, this study illuminates how different conformations and clusters of Env mediate HIV-1 Env–T cell interactions in real time and therefore might control immune evasion.

Atom‐by‐Atom Resolution of Structure–Function Relations over Low‐Nuclearity Metal Catalysts

AbstractControlling the structure sensitivity of catalyzed reactions over metals is central to developing atom‐efficient chemical processes. Approaching the minimum ensemble size, the properties enter a non‐scalable regime in which each atom counts. Almost all trends in this ultra‐small frontier derive from surface science approaches using model systems, because of both synthetic and analytical challenges. Exploiting the unique coordination chemistry of carbon nitride, we discriminate through experiments and simulations the interplay between the geometry, electronic structure, and reactivity of palladium atoms, dimers, and trimers. Catalytic tests evidence application‐dependent requirements of the active ensemble. In the semi‐hydrogenation of alkynes, the nuclearity primarily impacts activity, whereas the selectivity and stability are affected in Suzuki coupling. This powerful approach will provide practical insights into the design of heterogeneous catalysts comprising well‐defined numbers of atoms.

Atom-by-Atom Resolution of Structure-Function Relations over Low-Nuclearity Metal Catalysts.

Controlling the structure sensitivity of catalyzed reactions over metals is central to developing atom-efficient chemical processes. Approaching the minimum ensemble size, the properties enter a non-scalable regime in which each atom counts. Almost all trends in this ultra-small frontier derive from surface science approaches using model systems, because of both synthetic and analytical challenges. Exploiting the unique coordination chemistry of carbon nitride, we discriminate through experiments and simulations the interplay between the geometry, electronic structure, and reactivity of palladium atoms, dimers, and trimers. Catalytic tests evidence application-dependent requirements of the active ensemble. In the semi-hydrogenation of alkynes, the nuclearity primarily impacts activity, whereas the selectivity and stability are affected in Suzuki coupling. This powerful approach will provide practical insights into the design of heterogeneous catalysts comprising well-defined numbers of atoms.

Examination of the electronic structure of oxygen-containing PAH dimers and trimers

Interactions of oxygen with polynuclear aromatic hydrocarbons (PAH) can occur both in the flame and during oxidation of soot atmospherically. Past experimental measurements of PAH in soot samples collected either immediately after combustion, from the atmosphere, or in a flame show a variety of oxygen moieties within the PAH structures. This study investigated the electronic structure of oxygen-containing PAH to gain insight into their interaction with light both to better interpret spectroscopic measurements and to recognize the role of oxygen-containing PAH in atmospheric radiative forcing. Our research has shown that oxygen in ethers and hydroxyl moieties on PAH showed little change to the HOMO-LUMO gap (HLG), whereas ketones and aldehydes show a HLG decrease of 0.5 eV. The effect is enhanced when more than one ketone is present on a PAH molecule and further enhanced in subsequent dehydrogenation to a quinone-like structure. The presence of an oxygen-containing PAH with a ketone functional group in a dimer and trimer will substantially lower the HLG of the PAH stack. This may have a significant effect in the interaction of atmospheric soot with solar radiation.

Symmetry-adapted perturbation theory potential for the adenine dimer.

A new intermolecular interaction potential for the adenine dimer has been developed with the help of a combination of symmetry-adapted perturbation theory and density functional theory (DFT-SAPT). Supermolecular intermolecular interaction energy computations on hydrogen-bonded and stacked adenine dimers at B3LYP-D, MP2, SCS-MP2, SCS-MI-MP2 and CCSD(T) levels showed that DFT-SAPT is in a very good agreement with CCSD(T). The developed ab initio intermolecular potential has been used to predict the cluster structure of adenine dimers, trimers and tetramers. These global cluster optimizations reproduced adenine dimers reported in the literature and moreover new low-energy structures were also located. For trimers and tetramers, new hydrogen-bonded and stacked low-energy structures have also been found. The current findings suggest that the new ab initio potential can further be exploited to reveal the structure and energy of much larger supramolecular adenine clusters.

Elusive structure of helium trimers

Over the years many He–He interaction potentials have been developed, some very sophisticated, including various corrections beyond the Born–Oppenheimer approximation. Most of them were used to predict properties of helium dimers and trimers, examples of exotic quantum states, whose experimental study proved to be very challenging. Recently, detailed structural properties of helium trimers were measured for the first time, allowing a comparison with theoretical predictions and possibly enabling the evaluation of different interaction potentials. The comparisons already made included adjusting the maxima of both theoretical and experimental correlation functions to one, so the overall agreement between theory and experiment appeared satisfactory. However, no attempt was made to evaluate the quality of the interaction potentials used in the calculations. In this work, we calculate the experimentally measured correlation functions using both new and old potentials, compare them with experimental data and rank the potentials. We use diffusion Monte Carlo simulations at T = 0, which give within statistical noise exact results of the ground state properties. All models predict both trimers 4He3 and 4HeHe to be in a quantum halo state.

Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal of a Conserved CD4 Binding Site-Proximal Glycan.

The envelope glycoprotein (Env) is the major target for HIV-1 broadly neutralizing antibodies (bNAbs). One of the mechanisms that HIV has evolved to escape the host's immune response is to mask conserved epitopes on Env with dense glycosylation. Previous studies have shown that the removal of a particular conserved glycan at N197 increases the neutralization sensitivity of the virus to antibodies targeting the CD4 binding site (CD4bs), making it a site of significant interest from the perspective of vaccine design. At present, the structural consequences that result from the removal of the N197 glycan have not been characterized. Using native-like SOSIP trimers, we examine the effects on antigenicity and local structural dynamics resulting from the removal of this glycan. A large increase in the binding of CD4bs and V3-targeting antibodies is observed for the N197Q mutant in trimeric Env, while no changes are observed with monomeric gp120. While the overall structure and thermostability are not altered, a subtle increase in the flexibility of the variable loops at the trimeric interface of adjacent protomers is evident in the N197Q mutant by hydrogen-deuterium exchange mass spectrometry. Structural modeling of the glycan chains suggests that the spatial occupancy of the N197 glycan leads to steric clashes with CD4bs antibodies in the Env trimer but not monomeric gp120. Our results indicate that the removal of the N197 glycan enhances the exposure of relevant bNAb epitopes on Env with a minimal impact on the overall trimeric structure. These findings present a simple modification for enhancing trimeric Env immunogens in vaccines. The HIV-1 Env glycoprotein presents a dense patchwork of host cell-derived N-linked glycans. This so-called glycan shield is considered to be a major protective mechanism against immune recognition. While the positions of many N-linked glycans are isolate specific, some are highly conserved and are believed to play key functional roles. In this study, we examine the conserved, CD4 binding site-proximal N197 glycan and demonstrate that its removal both facilitates neutralizing antibody access to the CD4 binding site and modestly impacts the structural dynamics at the trimer crown without drastically altering global Env trimer stability. This indicates that surgical glycosylation site modification may be an effective way of sculpting epitope presentation in Env-based vaccines.

Structure of trimers of group-2B metal dihalides from relativistic density-functional calculations

We report density-functional calculations, carried out in a quantum-chemical approach using localised-Gaussians expansions of the Kohn–Sham orbitals, for metal dihalides trimers (MX2)3, where X = Cl, Br, or I and M = Zn, Cd, or Hg. The reliability of the method and the relevance of relativistic terms are assessed by comparisons with previous results on bond lengths in the monomer and dimer of these compounds. In a viewpoint regarding the trimer as a possible structural component of expanded liquid states and of compressed gaseous states, we stress the character of the local coordination of the metal ion in the ground state as being of a distorted tetrahedral type in the case of the trimer of the Zn and Cd dihalides and of a twofold type in the Hg dihalides. We also discuss the presence of metastable and unstable structures at higher energies and the quantum-chemical topology of the trimer.

Spin and orbital magnetism of coinage metal trimers (Cu3, Ag3, Au3): A relativistic density functional theory study

We have demonstrated electronic structure and magnetic properties of Cu3, Ag3 and Au3 trimers using a full potential local orbital method in the framework of relativistic density functional theory. We have also shown that the non-relativistic generalized gradient approximation for the exchange-correlation energy functional gives reliable magnetic properties in coinage metal trimers compared to experiment. In addition we have indicated that the spin-orbit coupling changes the structure and magnetic properties of gold trimer while the structure and magnetic properties of copper and silver trimers are marginally affected. A significant orbital moment of 0.21μB was found for most stable geometry of the gold trimer whereas orbital magnetism is almost quenched in the copper and silver trimers.

Physicochemical Studies of Bacteriorhodopsin Reconstituted in Partially Fluorinated Phosphatidylcholine Bilayers

A membrane protein bacteriorhodopsin (bR) that is successfully reconstituted in liposome of a novel partially fluorinated analog of dimyristoylphosphatidylcholine (DMPC) with the perfluorobutyl segments in the myristoyl groups, diF4H10-PC, has been investigated by some spectroscopic and X-ray diffraction techniques to clarify effects of substitution of nine hydrogen atoms by fluorine atoms on structural and physical properties of the membrane protein by comparison with the previous results on proteoliposome of bR and DMPC. Below the gel-to-liquid crystalline phase transition of diF4H10-PC bilayer, bR molecules adopt the two-dimensional lattice structure of trimers as the structural unit and show a photocycle very similar to that of native purple membrane like reconstituted bR in DMPC liposome in the gel phase. Even upon heating up to temperatures well above the phase transition, the nativelike functional reconstitution and higher structural stability of bR molecules in diF4H10-PC liposome are retained, which strikingly contrasts with lipid phase transition-induced disaggregation of protein molecules and light-induced denaturation in DMPC liposome. Greater membrane rigidity and low affinity between bR and fluorinated lipid molecules are proposed as a driving force for keeping nativelike properties of bR molecules in diF4H10-PC liposome even in the fluid phase.

Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies

Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that ∼75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.

Static and dynamic structure of monomers, dimers and trimers of HgCl2 from density-functional calculations

We report relativistic density-functional calculations for the equilibrium structures and the vibrational frequencies of the (HgCl2)n molecules with n = 1 to 3, as part of a broad exploration of the potential energy landscape of these compounds that will later be used to develop their pseudoclassical interatomic force laws. The calculations are carried out both in a physical plane-waves-expansion approach and in a quantum-chemical localized-Gaussians-expansion approach, with mutually consistent results within their expected accuracy, and are supplemented by analysis of the bond type and of the valence-electrons localization. The relativistic results are also compared with those of analogous non-relativistic calculations. For the monomer and the dimer we find close agreement with the earlier results of Kaupp and von Schnering and of Donald, Hargittai and Hoffmann, and in particular for the mechanical-equilibrium shape of the dimer we confirm their prediction of a major symmetry-breaking distortion driven by relativistic effects. We find an analogous relativistic structural distortion for the trimer, leading to alternative mechanical-equilibrium shapes that can all be viewed as resulting from the direct addition of a monomer to a dimer. The basic ground-state structures of the trimer clearly are precursors to the unique crystal structure of HgCl2 as a lamellar crystal formed from stripes of Cl-Hg-Cl molecules.

Structures of Aβ17–42 Trimers in Isolation and with Five Small-Molecule Drugs Using a Hierarchical Computational Procedure

The amyloid-β protein (Aβ) oligomers are believed to be the main culprits in the cytoxicity of Alzheimer's disease (AD) and p3 peptides (Aβ17-42 fragments) are present in AD amyloid plaques. Many small-molecule or peptide-based inhibitors are known to slow down Aβ aggregation and reduce the toxicity in vitro, but their exact modes of action remain to be determined since there has been no atomic level of Aβ(p3)-drug oligomers. In this study, we have determined the structure of Aβ17-42 trimers both in aqueous solution and in the presence of five small-molecule inhibitors using a multiscale computational study. These inhibitors include 2002-H20, curcumin, EGCG, Nqtrp, and resveratrol. First, we used replica exchange molecular dynamics simulations coupled to the coarse-grained (CG) OPEP force field. These CG simulations reveal that the conformational ensemble of Aβ17-42 trimer can be described by 14 clusters with each peptide essentially adopting turn/random coil configurations, although the most populated cluster is characterized by one peptide with a β-hairpin at Phe19-Leu31. Second, these 14 dominant clusters and the less-frequent fibril-like state with parallel register of the peptides were subjected to atomistic Autodock simulations. Our analysis reveals that the drugs have multiple binding modes with different binding affinities for trimeric Aβ17-42 although they interact preferentially with the CHC region (residues 17-21). The compounds 2002-H20 and Nqtrp are found to be the worst and best binders, respectively, suggesting that the drugs may interfere at different stages of Aβ oligomerization. Finally, explicit solvent molecular dynamics of two predicted Nqtrp-Aβ17-42 conformations describe at atomic level some possible modes of action for Nqtrp.