Helical Strands Research Articles

New Insights into the Dynamics and Energetics of Phage T4 Injection Machineray using a Continuum Model

Bacteriophage T4, from the family Myoviridae, is one of the most common tailed viruses that infects E.coli. Phage T4 is composed of three major protein structures; 1) a large capsid containing the viral genome, 2) a contractile tail structure connected to the capsid which generates the driving force to pierce the host membrane and conveys DNA from the capsid to the host, and 3) a baseplate equipped with fibers that recognize and bind to the host. The contractile tail consists of a rigid tail tube surrounded by an elastic six-helical-stranded sheath. During injection, the sheath undergoes a large conformational transition from a high-energy extended state to a low-energy contracted state, thereby releasing energy needed for the tail tube to penetrate the host. While the atomic structure of phage T4 is largely known, the dynamics of the injection process is not, including time scale and energetics of injection. To fill that gap, we propose a dynamic model of the entire phage T4 to simulate the dynamics of the injection process. The simulation follows in two stages; first, we employ molecular dynamic (MD) simulations to calculate the elastic stiffness constants and internal friction of the sheath strands. Second, we employ those material properties in a continuum model of the entire virus. The continuum model treats the tail sheath as a six-interacting elastic helical strands that are coupled to a massive cylinder representing the capsid and to a rigid rod representing the tail tube. The resulting model predicts that the driving energy of injection process is about 5500kT, the time scale of sheath contraction is on the order of milliseconds, and the internal friction of sheath strands is a main source of energy dissipation during sheath contraction.

Controlled Formation and Binding Selectivity of Discrete Oligo(methyl methacrylate) Stereocomplexes.

The triple-helix stereocomplex of poly(methyl methacrylate) (PMMA) is a unique example of a multistranded synthetic helix that has significant utility and promise in materials science and nanotechnology. To gain a fundamental understanding of the underlying assembly process, discrete stereoregular oligomer libraries were prepared by combining stereospecific polymerization techniques with automated flash chromatography purification. Stereocomplex assembly of these discrete building blocks enabled the identification of (1) the minimum degree of polymerization required for the stereocomplex formation and (2) the dependence of the helix crystallization mode on the length of assembling precursors. More significantly, our experiments resolved binding selectivity between helical strands with similar molecular weights. This presents new opportunities for the development of next-generation polymeric materials based on a triple-helix motif.

Maximization of the tensile stiffness for helical strands

Maximization of the tensile stiffness for helical strands

Finite element modeling of the elastoplastic axial-torsional response of helical constructions to traction loads

In the current work, we present a planar elastoplastic finite element model for the simulation of the mechanical response of helical constructions to traction loads. We elaborate a numerical scheme that employs a detailed description of the helical geometry and characterizes its coupled axial and torsional response. We validate the modelling results with well-established three-dimensional (3D) finite element schemes. For the validation, a single layer helical strand with different construction parameters is employed. Additional analysis is carried out to highlight the role of hardening, providing useful insights in the effect of loading history on the structure’s macroscopic elastoplastic response. Overall, a low computation cost elastoplastic modeling scheme, suitable for large-scale structural analysis of helical constructions is presented.

Wind-Tunnel Experiments on Vortex-Induced Vibration of Rough Bridge Cables

Surface roughness, ice accretion, and atmospheric turbulence are important issues because they can considerably alter the aerodynamic characteristics of bridge cables. The present study describes wind-tunnel experiments on vortex-induced vibrations of rough bridge cables characterized with various surface roughness and performed at various levels of atmospheric turbulence. Three different cable models were used: a smooth cylinder to represent dry cables, a helical strand cable, and a cable with modeled ice accretion. The studied parameters include the critical velocity and amplitude of vortex-induced vibration and parameter sensitivity to changes in flow turbulence and cable surface roughness. The results obtained indicate that cable roughness and turbulence of the flow have significant influences on the dynamic response of bridge cables. The experimental results indicate that the vortex-induced vibration was largest for the ice-accreted bridge cable.

Simplified elastic wave modeling in seven-wire prestressed parallel strands

This paper considers elastic wave propagation in seven-wire parallel strands. Under a transverse distributed force, the stress state of seven-wire strands is derived from the Hertzian theory, which is regarded as the prestress state for the dynamic analysis. According to the wave finite element method, the elastodynamic equation with prestress is discretized corresponding to harmonic wave motion. Firstly, the results are verified by the semi-analysis finite element method. Then, dispersion properties in seven-wire parallel strands are computed and compared to those of double cylindrical rods. Besides, the results from parallel strands and helical strands indicate that wave propagation in the former is significantly different from that in the latter. For the deep understanding of wave characteristics, the displacement vectors are used to identify the propagating modes. It is found that there is only one torsional-like mode which rotates with a twist center in the whole region. Meanwhile, it is found that the variation of prestress has large influence on the torsional-like mode for low frequencies, but little on propagating modes for high frequencies. In addition, there appears the notch frequency and the effect of prestress on it is discussed in detail. The notch frequency decreases with the rising of the prestress in a certain range.

Self‐Assembly of Conjugated Metallopolymers with Tunable Length and Controlled Regiochemistry

AbstractSelf‐assembled materials can be designed to express useful optoelectronic properties; however, achieving structural control is a necessary precondition for the optimization of desired properties. Here we report a simple, metal‐templated polymerization process that generates helical metallopolymer strands over 75 repeat units long (28 kDa) from a single bifunctional monomer and CuI. The resulting polymer consists of a double helix of two identical conjugated organic strands enclosing a central column of metal ions. The length of this metallopolymer can be controlled by adding monofunctional subcomponents to end‐cap the conjugated ligands. The use of ditopic and bulky monotopic subcomponents, respectively, allows a head‐to‐head or head‐to‐tail double helix to be generated. Spectroscopic measurements of different polymer lengths demonstrate how control over polymer length leads to control over the electronic and luminescent properties of the resulting material, thereby enabling tunable white‐light emission.

Self-Assembly of Conjugated Metallopolymers with Tunable Length and Controlled Regiochemistry.

Self-assembled materials can be designed to express useful optoelectronic properties; however, achieving structural control is a necessary precondition for the optimization of desired properties. Here we report a simple, metal-templated polymerization process that generates helical metallopolymer strands over 75 repeat units long (28 kDa) from a single bifunctional monomer and CuI . The resulting polymer consists of a double helix of two identical conjugated organic strands enclosing a central column of metal ions. The length of this metallopolymer can be controlled by adding monofunctional subcomponents to end-cap the conjugated ligands. The use of ditopic and bulky monotopic subcomponents, respectively, allows a head-to-head or head-to-tail double helix to be generated. Spectroscopic measurements of different polymer lengths demonstrate how control over polymer length leads to control over the electronic and luminescent properties of the resulting material, thereby enabling tunable white-light emission.

Cooperativity of myosin interaction with thin filaments is enhanced by stabilizing substitutions in tropomyosin.

Muscle contraction is powered by myosin interaction with actin-based thin filaments containing Ca2+-regulatory proteins, tropomyosin and troponin. Coiled-coil tropomyosin molecules form a long helical strand that winds around actin filament and either shields actin from myosin binding or opens it. Non-canonical residues G126 and D137 in the central part of tropomyosin destabilize its coiled-coil structure. Their substitutions for canonical ones, G126R and D137L, increase structural stability and the velocity of sliding of reconstructed thin filaments along myosin coated surface. The effect of these stabilizing mutations on force of the actin-myosin interaction is unknown. It also remains unclear whether the stabilization affects single actin-myosin interactions or it modifies the cooperativity of the binding of myosin molecules to actin. We used an optical trap to measure the effects of the stabilization on step size, unitary force and duration of the interactions at low and high load and compared the results with those obtained in an in vitro motility assay. We found that significant prolongation of lifetime of the actin-myosin complex under high load observed at high extent of tropomyosin stabilization, i.e. with double mutant, G126R/D137L, correlates with higher force in the motility assay. Also, the higher the extent of stabilization of tropomyosin, the fewer myosin molecules are needed to propel the thin filaments. The data suggest that the effects of the stabilizing mutations in tropomyosin on the myosin interaction with regulated thin filaments are mainly realized via cooperative mechanisms by increasing the size of cooperative unit.

The Closed State of the Thin Filament Is Not Occupied in Fully Activated Skeletal Muscle

Muscle contraction is powered by actin-myosin interaction controlled by Ca2+ via the regulatory proteins troponin (Tn) and tropomyosin (Tpm), which are associated with actin filaments. Tpm forms coiled-coil dimers, which assemble into a helical strand that runs along the whole ∼1 μm length of a thin filament. In the absence of Ca2+, Tn that is tightly bound to Tpm binds actin and holds the Tpm strand in the blocked, or B, state, where Tpm shields actin from the binding of myosin heads. Ca2+ binding to Tn releases the Tpm from actin so that it moves azimuthally around the filament axis to a closed, or C, state, where actin is partially available for weak binding of myosin heads. Upon transition of the weak actin-myosin bond into a strong, stereo-specific complex, the myosin heads push Tpm strand to the open, or O, state allowing myosin binding sites on several neighboring actin monomers to become open for myosin binding. We used low-angle x-ray diffraction at the European Synchrotron Radiation Facility to check whether the O- to C-state transition in fully activated fibers of fast skeletal muscle of the rabbit occurs during transition from isometric contraction to shortening under low load. No decrease in the intensity of the second actin layer line at reciprocal radii in the range of 0.15–0.275 nm−1 was observed during shortening suggesting that an azimuthal Tpm movement from the O- to C-state does not occur, although during shortening muscle stiffness is reduced compared to the isometric state, and the intensities of other actin layer lines demonstrate a ∼2-fold decrease in the fraction of myosin heads strongly bound to actin. The data show that a small fraction of actin-bound myosin heads is sufficient for supporting the O-state and, therefore the C-state is not occupied in fully activated skeletal muscle that produces mechanical work at low load.

Achiral polyamine-induced chiral zinc gallophosphates with fused double helix-like strands exhibiting blue to green photoluminescence.

This study found non-chiral polyamines to be effective in inducing chiral frameworks. Four zinc gallophosphates with a chiral UCSB-7 topology were generated from the use of four different linear-chain polyamines as templates. In the structure, helical inorganic strands and templates appeared to fuse into a double helix-like arrangement. Notably, they are the first chiral frameworks to display optical analogues and intriguing photoluminescence properties.

Synthesis, characterization, crystal structures and supramolecular features of bicycloazastannoxides derived from Schiff bases with L-tyrosine

Six new bicycloazastannoxides of compositions [Me2Sn(L1H)] (1), [nBu2Sn(L1H)] (2), [Ph2Sn(L1H)] (3), [Bz2Sn(L1H)] (4), [Me2Sn(L2H)(MeOH)]·MeOH (5) and [Ph2Sn(L3H)] (6), where L1H = 2-((E)-((Z)-4-hydroxypent-3-en-2-ylidene)amino)-3-(4-hydroxyphenyl)propanoate, L2H = (E)-2-((2-hydroxybenzylidene)amino)-3-(4-hydroxyphenyl)propanoate and L3H = (E)-3-(4-hydroxyphenyl)-2-((1-(2-hydroxyphenyl)ethylidene)amino)propanoate, were synthesized and spectroscopically characterized. The 1H and 13C NMR spectra of compounds 1–6 displayed two sets of signals for Sn-R2 (R = Me, nBu, Ph and Bz) indicating a diastereotopic environment according to the asymmetric nature of the ligand. The 119Sn NMR data of the compounds in CDCl3 indicate five-coordinate tin atoms, showing that the bicycloazastannoxide assemblies remain intact as observed in the solid-state structures. The crystal structures of 1–6 revealed discrete molecular structures in all cases with distorted trigonal-bipyramidal geometries for 1–4 and 6, and a strongly distorted six-fold coordination for 5 due to association of a MeOH solvent molecule. At the supramolecular level, the molecular structures in 1–4 and 6 are linked either through double-bridged O-H⋯O/C-H⋯O synthons (1 and 6) or single O-H⋯O hydrogen bonds (2–4). The resulting 1D helical strands exhibit varying Sn⋯Sn distances due to the different molecular conformations. The molecules in 5 associate to dimers through two Sn⋯O and O-H⋯O interactions, which are further connected via O-H⋯O hydrogen bonds to give 1D strands containing 22-membered macrocycles.

Structure Direction, Solvent Effects, and Anion Influences in Halogen-Bonded Adducts of 2,6-Bis(iodoethynyl)pyridine

A new divergent and self-complementary halogen bond donor–acceptor molecule 2,6-bis(iodoethynyl)pyridine L has been prepared and structurally characterized, and used to generate a series of extended halogen-bonded adducts with tetrabutylammonium halide salts. The reaction between L and anions such as either bromide or chloride gives the one-dimensional polymeric species {L·TBABr} or {L·TBACl}, respectively, which contains helical strands linked by C–I···X– halogen bonds which partially encapsulate the associated organic cations. Varying the reaction solvent from ethyl acetate to 5:95 methanol/ethyl acetate gives rise to another polymeric phase on combining L with tetrabutylammonium chloride, the one-dimensional looped chain structure {L2·TBACl} in which each chloride ion acts as a four-connected square planar node for halogen bonding interactions originating from L. Similar solvent effects are observed in the discrete macrocyclic species {L·TBAI}-α and {L·TBAI}-β, both consisting of cyclic (L2I2)2– specie...

Creating complex molecular topologies by configuring DNA four-way junctions.

The realization of complex topologies at the molecular level represents a grand challenge in chemistry. This necessitates the manipulation of molecular interactions with high precision. Here we show that single-stranded DNA (ssDNA) knots and links can be created by utilizing the inherent topological properties that pertain to the DNA four-way junction, at which the two helical strands form a node and can be configured conveniently and connected for complex topological construction. Using this strategy, we produced series of ssDNA topoisomers with the same sequences. By finely designing the curvature and torsion, double-stranded DNA knots were accessed by hybridizing and ligating the complementary strands with the knotted ssDNA templates. Furthermore, we demonstrate the use of a constructed ssDNA knot both to probe the topological conversion catalysed by DNA topoisomerase and to study the DNA replication under topological constraint.

Toluene promotes lid 2 interfacial activation of cold active solvent tolerant lipase from Pseudomonas fluorescens strain AMS8

The utilization of cold active lipases in organic solvents proves an excellent approach for chiral synthesis and modification of fats and oil due to the inherent flexibility of lipases under low water conditions. In order to verify whether this lipase can function as a valuable synthetic catalyst, the mechanism concerning activation of the lid and interacting solvent residues in the presence of organic solvent must be well understood. A new alkaline cold-adapted lipase, AMS8, from Pseudomonas fluorescens was studied for its structural adaptation and flexibility prior to its exposure to non-polar, polar aprotic and protic solvents. Solvents such as ethanol, toluene, DMSO and 2-propanol showed to have good interactions with active sites. Asparagine (Asn) and tyrosine (Tyr) were key residues attracted to solvents because they could form hydrogen bonds. Unlike in other solvents, Phe-18, Tyr-236 and Tyr-318 were predicted to have aromatic-aromatic side-chain interactions with toluene. Non-polar solvent also was found to possess highest energy binding compared to polar solvents. Due to this circumstance, the interaction of toluene and AMS8 lipase was primarily based on hydrophobicity and molecular recognition. The molecular dynamic simulation showed that lid 2 (residues 148–167) was very flexible in toluene and Ca2+. As a result, lid 2 moves away from the catalytic areas, leaving an opening for better substrate accessibility which promotes protein activation. Only a single lid (lid 2) showed the movement following interactions with toluene, although AMS8 lipase displayed double lids. The secondary conformation of AMS8 lipase that was affected by toluene observed a reduction of helical strands and increased coil structure. Overall, this work shows that cold active lipase, AMS8 exhibits distinguish interfacial activation and stability in the presence of polar and non-polar solvents.

A First Model of the Dynamics of the Bacteriophage T4 Injection Machinery

Bacteriophage T4 is one of the most common and complex of the tailed viruses that infect host bacteria using an intriguing contractile tail assembly. Despite extensive progress in resolving the structure of T4, the dynamics of the injection machinery remains largely unknown. This paper contributes a first model of the injection machinery that is driven by elastic energy stored in a structure known as the sheath. The sheath is composed of helical strands of protein that suddenly collapse from an energetic, extended conformation prior to infection to a relaxed, contracted conformation during infection. We employ Kirchhoff rod theory to simulate the nonlinear dynamics of a single protein strand coupled to a model for the remainder of the virus, including the coupled translation and rotation of the head (capsid), neck, and tail tube. Doing so provides an important building block toward the future goal of modeling the entire sheath structure which is composed of six interacting helical protein strands. The resulting numerical model exposes fundamental features of the injection machinery including the time scale and energetics of the infection process, the nonlinear conformational change experienced by the sheath, and the contribution of hydrodynamic drag on the head (capsid).

Use of molecular dynamics simulation to explore structural facets of human prion protein with pathogenic mutations

Prion diseases are caused by mutations at different positions of the prion protein. A large number of pathogenic mutations are reported in the literature. Two of such point mutations T193I and R148H located at two different helical strands (H2 and H1) of the prion protein associated with fCJD (familial Creutzfeld–Jacob disease) are studied. We have used classical molecular dynamics (MD) simulation technique to understand the conformational changes and dynamics of the protein under the effect of mutation and compared with the native prion protein. The results indicate that: both mutated forms are conformationally steadier than the native prion protein; although there are no major conformational transitions, R148H leads to decreased native β-sheet content, H1 helix becomes less fluctuating, two new turn regions appear and conversion of a 310 region to coil form takes place. Mutation T193I leads to a steady H1 helix, a decreased native β-sheet content and a new 310 region appears in H2 helix. Moreover, mutation R148H results in decreased conformational space with a highly compact and nonfluctuating form.

Secondary Structures in Inorganic Helicates of an Octadentate Phenanthroline‐Type Schiff Base Ligand

AbstractTo analyze the contribution of supramolecular interactions to helical architectures and to investigate whether ligand folding can be induced by only protons in a similar fashion in the absence of metal ions, a new 1,10‐phenanthroline (phen)‐based extended ligand, C12H6N2[CHNC6H4NH(C10H6N)]2 (L1), its copper(I) complexes, [Cu2(C12H6N2{CHNC6H4NH(C10H6N)}2)2] [PF6]2 (1), [Cu2(C12H6N2{CHNC6H4NH(C10H6N)}2)2][BF4]2 (2), [Cu2(C12H6N2{CHNC6H4NH(C10H6N)}2)2][CuCl2]2·CH2Cl2 (3), and [Cu4(C12H6N2{CHNC6H4NH(C10H6N)}2)2][Cu2I4] (4), were prepared and structurally characterized. Ligand L1 wraps copper(I) ions in two intriguingly different fashions depending on the nature of the anions. Although dicopper helicates 1–3 and tetracopper helicate 4 show significant intermolecular interactions that show considerable structural relationships with DNA, helicate 4 more closely resembles the structural features of DNA that even phen‐based stacking interactions are present between the two helical strands. In complex 4, the dinuclear [Cu2I4]2– dianion is involved in intermolecular interactions, which joins two cationic units in a linear fashion, whereas the monoanions in complexes 1–3 (i.e., PF6–, BF4–, and CuCl2–) are only involved in intramolecular interactions or connect the cations laterally. The anion‐dependent topology serves as a reminder that the helical topology of a cation can be altered by changing the nature of the anion.

Numerical geometry of map and model assessment.

We are describing best practices and assessment strategies for the atomic interpretation of cryo-electron microscopy (cryo-EM) maps. Multiscale numerical geometry strategies in the Situs package and in secondary structure detection software are currently evolving due to the recent increases in cryo-EM resolution. Criteria that aim to predict the accuracy of fitted atomic models at low (worse than 8Å) and medium (4-8 Å) resolutions remain challenging. However, a high level of confidence in atomic models can be achieved by combining such criteria. The observed errors are due to map-model discrepancies and due to the effect of imperfect global docking strategies. Extending the earlier motion capture approach developed for flexible fitting, we use simulated fiducials (pseudoatoms) at varying levels of coarse-graining to track the local drift of structural features. We compare three tracking approaches: naïve vector quantization, a smoothly deformable model, and a tessellation of the structure into rigid Voronoi cells, which are fitted using a multi-fragment refinement approach. The lowest error is an upper bound for the (small) discrepancy between the crystal structure and the EM map due to different conditions in their structure determination. When internal features such as secondary structures are visible in medium-resolution EM maps, it is possible to extend the idea of point-based fiducials to more complex geometric representations such as helical axes, strands, and skeletons. We propose quantitative strategies to assess map-model pairs when such secondary structure patterns are prominent.

Helical Defect Packings in a Quasi-One-Dimensional System of Cylindrically Confined Hard Spheres.

We use a combination of analytical theory and molecular dynamics simulation to study the inherent structure landscape of a system of hard spheres confined to narrow cylindrical channels of diameter 1+√[3]/2<H(d)/σ<1+4√[3]/7. The most dense packing is a perfect, symmetrical single helix. The presence of topological defects that change the local chirality of the helix lowers the packing density and alters the local packing structure. The helical sections between defects become asymmetrical and are better described as a double helix with angular twists between the first and second nearest neighbors that are determined by the defect separation distance. Increasing the fraction of defects unwinds the two helical strands so that the least dense structure is a nonhelical packing of two zigzag chains. We also show that the packing effects of the helical section induce a long-range, entropically driven attraction between the defects.