Groove Of Helix Research Articles

Induced Self-Assembly of Vitamin E-Spermine/siRNA Nanocomplexes via Spermine/Helix Groove-Specific Interaction for Efficient siRNA Delivery and Antitumor Therapy.

Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self-assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E-spermine/siRNA complexes can further self-assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self-assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE-Su-Sper/DSPE-PEG2000/siSurvivin self-assembled nanocomplexes can accumulate in cancer cells and gradually release siRNA in tumor tissues and show significant antitumor effect in vivo. The self-assembled delivery system provides a novel strategy for highly efficient siRNA delivery.

Sequence-Dependent Orientational Coupling and Electrostatic Attraction in Cation-Mediated DNA-DNA Interactions.

Condensation of DNA is vital for its biological functions and controlled nucleic acid assemblies. However, the mechanisms of DNA condensation are not fully understood due to the inability of experiments to access cation distributions and the complex interplay of energetic and entropic forces during assembly. By constructing free energy surfaces using exhaustive sampling and detailed analysis of cation distributions, we elucidate the mechanism of DNA condensation in different salt conditions and with different DNA sequences. We found that DNA condensation is facilitated by the correlated dynamics of the localized cations at the grooves of DNA helices. These dynamics are strongly dependent on the salt conditions and DNA sequences. In the presence of magnesium ions, major groove binding facilitates attraction. In contrast, in the presence of polyvalent cations, minor groove binding serves to create charge patterns, leading to condensation. Our findings present a novel advancement in the field and have broad implications for understanding and controlling nucleic acid complexes in vivo and in vitro.

Axial Motion Characterization of a Helical Ionic Polymer Metal Composite Actuator and Its Application in 3-DOF Micro-Parallel Platforms

In this work, a helical ionic polymer metal composite (IPMC) was fabricated by thermal treatment in a mold with helix grooves. The axial actuation behaviors of the helical IPMC actuator were observed, and the electromechanical and electrochemical characteristics were evaluated. The experimental results showed that as the voltage increased and the frequency decreased, the axial displacement, axial force, and electric current of the actuator all increased. Compared with square wave and sinusoidal signals, the actuator exhibited the most satisfactory motion under the direct current (DC) signal. For the electrochemical test, as the scanning rate decreased, the gravimetric specific capacitance increased. Within a suitable voltage range, the actuator was chemically stable. In addition, we coupled the Electrostatics module, Transport of Diluted Species module, and Solid Mechanics module in COMSOL Multiphysics software to model and analyze the helical IPMC actuator. The simulation data obtained were in good agreement with the experimental data. Finally, by using three helical IPMC actuators as driving components, an innovative three-degree-of-freedom (3-DOF) micro-parallel platform was designed, and it could realize a complex coupling movement of pitch, roll, and yaw under the action of an electric field. This platform is expected to be used in micro-assembly, flexible robots, and other fields.

Investigation on fluid field characteristics and cinders transport laws in the annulus of grooved drill pipe based on two-phase flow model

Despite the grooved drill pipe (GDP) has been applied in the soft coal seam in recent years, it remains unclear of the cinders transport mechanism in the annulus of GDP. In this study, the cinders transport model of GDP was developed based on an improved method, combining the kinetic theory of granular flow and Eulerian-Eulerian two-phase flow model. The annular fluid field characteristics and cinders transport laws of GDP were studied in this model by considering drag force, lift force, and virtual mass force. Finally, the precision of this model was verified via the experimental data. The results show that the annular velocity and cinders distribution present periodic variations with the drill pipe pitch. A role of guiding and tangential force on fluid field by the helix grooves is found. The volume fraction of residual cinders is dramatically reduced from 0.144 to 0.085 as the inlet velocity increases from 0.6 m/s to 1.2 m/s. This indicates the performance of cinders transport can be improved by increasing inlet velocity of drilling fluid.

Anion effect of Cl−, I−, and F− on counterions condensation within nucleic acid ion atmosphere

In the present work, molecular dynamics simulations have been carried out to study the anion effect on counterions distribution around the DNA double helix on the character of ion hydration. The simulated systems consisted of DNA fragment d(CGCGAATTCGCG) in water solution with the counterions and anions Cl−, I− or F−. Ion distribution and the characteristic binding sites of the counterions with DNA have been determined. The results show that due to the interaction with anions average number of counterions nearly DNA surface undergo changes. The amount of Na+ experienced a decline and the number of K+ experienced an increase with the change of Cl−, I−, and F− anion environment, while Na+ content remained at a high level compared with K+, anions are less present near DNA. Due to the dehydration effect, smaller Na+ counterions can squeeze through the hydration shell of DNA to the bottom of the double helix grooves. Two counterions are mainly indirect binding DNA, which prefer to bind at the phosphate backbone compared to the major groove and negligible binding occurs in the minor groove. The K+ counterions show stronger ability to cluster with anions thus more likely to be shielded from DNA electrostatic field. The character of ion size, ion-DNA interaction, and the ion hydration establishes the correlation between the counterions and anions within nucleic acid ion atmosphere.

Investigation and optimization on cooling performance of a novel double helix structure for cylindrical lithium-ion batteries

Abstract Liquid cooling system was critical to keep the performance of lithium-ion battery due to its good conductivity to keep battery working in a cool environment. In this study, a novel double helix cooling structure was designed for an 18650 lithium battery. The numerical simulation was carried out to investigate the effects of the coolant mass flow rate (M), helix groove pitch (P) and flow diameter (D) on cooling performance. The design points obtained by Latin hypercube sampling were calculated numerically. Kriging approximate model method was adopted to reduce computing time. Using Non-dominated Sorting Genetic Algorithm II obtained the Pareto solution, and the multiple criteria decision making (MCDM) algorithm was used to sort the optimal solution set. The results showed that increasing mass flow rate can effectively lower the maximum temperature and temperature difference of the battery within a certain range of mass flow rate. When the mass flow rate increased to a certain value, the benefit from increasing the mass flow was limited. And the pitch and diameter would also have a tendency to the decrease of the maximum temperature or even the opposite result when they exceeded a certain value. The best cooling performance can be obtained when the mass flow rate is 1.94 × 10−3 kg/s, the pitch is 100 mm and the diameter is 0.4 mm. The novel cooling structure proposed in this study can provided a new approach for the structure design of the liquid-cooled cylindrical battery thermal management system.

Immunoinformatics Based Vaccine Design for Zea M 1 Pollen Allergen

Objective: Zea m1 is one of the most common aeroallergens, causing allergy. This pollen allergen, present in maize, is responsible for type I hypersensitivity reaction. Despite having available X ray crystal structure of this pollen allergen, no definite vaccine has been developed for allergic disorder in humans. Method: In our present study, an epitope-based peptide vaccine against Zea m 1 pollen allergen, using a combination of B cell and T cell epitope predictions, followed by molecular docking and molecular dynamics simulation methods are carried out. Here, protein sequences of homologous pollen allergens of Zea m1 are collected and conserved regions present in them are investigated. Result: From the identified region of the allergenic protein, the peptide sequence KVPPGPNITTNY and the sequence AEWKPMKLSM are considered as the most potential B cell and T cell epitopes respectively. Furthermore, this predicted T cell epitope AEWKPMKLSM interacted with MHC allelic protein HLAB* 44:02 with the lowest IC 50 value (7.94 nM). This epitope perfectly fitted into the epitope binding groove of alpha helix of MHC I molecule with lowest energy weighted score -620.0, showing stability in MHC binding. This epitope also showed a good conservancy of 69.75% in world population coverage. Conclusion: The epitopes KVPPGPNITTNY and AEWKPMKLSM may be considered as potential peptide for peptide vaccine for pollen allergen after further experimental study. Key words: Immunoinformatics, Vaccine design, Zea m1 pollen allergen, B cell epitope, T cell epitope, Molecular docking, Molecular dynamics.

Hydration of counterions interacting with DNA double helix: a molecular dynamics study.

In the present work, molecular dynamics simulations have been carried out to study the dependence of counterion distribution around the DNA double helix on the character of ion hydration. The simulated systems consisted of DNA fragment d(CGCGAATTCGCG) in water solution with the counterions Na+, K+, Cs+ or Mg2+. The characteristic binding sites of the counterions with DNA and the changes in their hydration shell have been determined. The results show that due to the interaction with DNA at least two hydration shells of the counterions undergo changes. The first hydration shell of Na+, K+, Cs+, and Mg2+ counterions in the bulk consists of six, seven, ten, and six water molecules, respectively, while the second one has several times higher values. The Mg2+ and Na+ counterions, constraining water molecules of the first hydration shell, mostly form with DNA water-mediated contacts. In this case the coordination numbers of the first hydration shell do not change, while the coordination numbers of the second one decrease about twofold. The Cs+ and K+ counterions that do not constrain surrounding water molecules may be easily dehydrated, and when interacting with DNA their first hydration shell may be decreased by three and five water molecules, respectively. Due to the dehydration effect, these counterions can squeeze through the hydration shell of DNA to the bottom of the double helix grooves. The character of ion hydration establishes the correlation between the coordination numbers of the first and the second hydration shells. Graphical Abstract Hydration of counterions interacting with DNA double helix.

The Solution Design of Hobbing Worm Milling Cutters Face Teeth Undercut

Face teeth grinding of special tools, as hobing worm milling cutters are, is the shape and cinematically complex operation with the respect to achieving the necessary accuracy and resultant shape geometry. The grinding wheel shape, it ́s size and the control helix angle of hobing worm are the primary factors which are compelling the ground groove accuracy during the face teeth sharpening process. Inappropriately selected combination of these parameters causes undercut of this surface and the negative impact on required accuracy. The main aim of the solution is to find a variable and to create a parametric mathematical model to calculate appropriate grinding wheel shape according to the input factors – hobing worm and grinding wheel parameters which affects this issue. This system will be used to create the initial grinding wheel surface and a helix groove undercut calculation program. The graphical part of this programme will be the next benefit.

Bioinformatical analysis of eukaryotic shugoshins reveals meiosis-specific features of vertebrate shugoshins.

BackgroundShugoshins (SGOs) are proteins that protect cohesins located at the centromeres of sister chromatids from their early cleavage during mitosis and meiosis in plants, fungi, and animals. Their function is to prevent premature sister-chromatid disjunction and segregation. The study focused on the structural differences among SGOs acting during mitosis and meiosis that cause differences in chromosome behavior in these two types of cell division in different organisms.MethodsA bioinformatical analysis of protein domains, conserved amino acid motifs, and physicochemical properties of 32 proteins from 25 species of plants, fungi, and animals was performed.ResultsWe identified a C-terminal amino acid motif that is highly evolutionarily conserved among the SGOs protecting centromere cohesion of sister chromatids in meiotic anaphase I, but not among mitotic SGOs. This meiotic motif is arginine-rich in vertebrates. SGOs differ in different eukaryotic kingdoms by the sets and locations of amino acid motifs and the number of α-helical regions in the protein molecule.DiscussionThese structural differences between meiotic and mitotic SGOs probably could be responsible for the prolonged SGOs resistance to degradation during meiotic metaphase I and anaphase I. We suggest that the “arginine comb” in C-end meiotic motifs is capable of interaction by hydrogen bonds with guanine bases in the minor groove of DNA helix, thus protecting SGOs from hydrolysis. Our findings support independent evolution of meiosis in different lineages of multicellular organisms.

Asymmetric cryo-EM structure of the canonical Allolevivirus Qβ reveals a single maturation protein and the genomic ssRNA in situ

Single-stranded (ss) RNA viruses infect all domains of life. To date, for most ssRNA virions, only the structures of the capsids and their associated protein components have been resolved to high resolution. Qβ, an ssRNA phage specific for the conjugative F-pilus, has a T = 3 icosahedral lattice of coat proteins assembled around its 4,217 nucleotides of genomic RNA (gRNA). In the mature virion, the maturation protein, A2, binds to the gRNA and is required for adsorption to the F-pilus. Here, we report the cryo-electron microscopy (cryo-EM) structures of Qβ with and without symmetry applied. The icosahedral structure, at 3.7-Å resolution, resolves loops not previously seen in the published X-ray structure, whereas the asymmetric structure, at 7-Å resolution, reveals A2 and the gRNA. A2 contains a bundle of α-helices and replaces one dimer of coat proteins at a twofold axis. The helix bundle binds gRNA, causing denser packing of RNA in its proximity, which asymmetrically expands the surrounding coat protein shell to potentially facilitate RNA release during infection. We observe a fixed pattern of gRNA organization among all viral particles, with the major and minor grooves of RNA helices clearly visible. A single layer of RNA directly contacts every copy of the coat protein, with one-third of the interactions occurring at operator-like RNA hairpins. These RNA-coat interactions stabilize the tertiary structure of gRNA within the virion, which could further provide a roadmap for capsid assembly.

Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome

The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.

Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors.

The human papillomavirus (HPV) HPV E6 protein has emerged as a central oncoprotein in HPV-associated cancers in which sustained expression is required for tumor progression. A majority of the E6 protein interactions within the human proteome use an alpha-helix groove interface for binding. The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface. This enables formation of a trimeric complex with p53, resulting in destruction of this tumor suppressor. While recent x-ray crystal structures are useful, examples of small molecule probes that can modulate protein interactions at this interface are limited. To develop insights useful for potential structure-based design of ligands for HPV E6, a series of 2,6-disubstituted benzopyranones were prepared and tested as competitive antagonists of E6-E6AP helix-groove interactions. These small molecule probes were used in both binding and functional assays to evaluate recognition features of the E6 protein. Evidence for an ionic functional group interaction within the helix groove was implicated by the structure-activity among the highest affinity ligands. The molecular topographies of these protein-ligand interactions were evaluated by comparing the binding and activities of single amino acid E6 mutants with the results of molecular dynamic simulations. A group of arginine residues that form a rim-cap over the E6 helix groove offer compensatory roles in binding and recognition of the small molecule probes. The flexibility and impact on the overall helix-groove shape dictated by these residues offer new insights for structure-based targeting of HPV E6.

Performance analysis of micro drill bit with asymmetric helix groove

Purpose – The purpose of this paper is to present a new method to optimize the micro drill bit based on finite element analysis, and analyze the performance of the asymmetric helix groove micro drill bit and provide a way to conduct the optimization of micro drill bits. Design/methodology/approach – First, the stress and deform of the micro drills were analyzed in ANSYS. Second, the influence of helix angle, web thickness and ratio of flute to land on stiffness was explored. Combining the former two results, a better set of parameters were optimized. Third, the modal analysis and harmonic response analysis of the optimized micro drill bit were analyzed in ANSYS. Finally, an experiment was carried out to verify the performance of the asymmetric helix groove micro drill bit. Findings – The stress and deform of the asymmetric helix groove micro drill bit are not symmetric. The rigidity is getting better with the web thickness increasing in the selected range; while, the rigidity is getting worse with the helix angle and ratio of flute to land increasing in the selected range. The natural frequencies of the optimized micro drill bit are far away from the excitation frequency, and the response displacement is very small under the excitation of the spindle. In the drilling experiment, the optimized micro drill bit performs well. Research limitations/implications – In this paper, the diameter of the asymmetric helix groove micro drill bit was 0.3 mm and the cross-section shape was not considered. The future research work should consider different diameters and cross-section shapes. Originality/value – Analyzing the influence of three main geometry parameters on the rigidity in ANSYS, a better set of parameters were optimized from the analysis results. The drilling experimental results show that this method is of great significance for obtaining the appropriate parameters of asymmetric helix groove micro drill bits.

Spectroscopic and molecular docking studies on the interaction of the drug olanzapine with calf thymus DNA

The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH<0 and ΔS<0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb=2×103M−1). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.

Fine DNA structure revealed by constant height frequency modulation AFM imaging

Few examples of sub nanometer resolution on biomolecules can be found in literature. In particular, AFM experiments on DNA mostly fail to show the double helical groove periodicity, and so far such a feat was only achieved in liquid. Here we describe a method that produces highly resolved images of DNA where contrast can be assigned to submolecular features such as DNA helix’s grooves. Two types of AFM experiments are presented: (1) We started by imaging DNA with Frequency Modulation (FM) AFM, where a shift in resonance frequency is used as a feedback signal and maintained constant during imaging. With FM-AFM we performed experiments in the non-contact (NC) mode, with z-feedback on, where only gentle (few tens of pN) non compressive force is applied between the tip and the sample. (2) Then we switched off the z-feedback and scanned the DNA sample at constant height measuring frequency modulation in order to acquire frequency shift maps of the sample. This was done at several separations including the distances where the frequency feedback is not stable due to the non-monotonicity of the frequency shift curve. At this distance sub-molecular resolution was reached and a calculation of the tip-sample van der Waals interaction at constant height, as well as the periodicity of the observed features that ranges from 3 to 5nm, suggest that these correspond to the DNA helix grooves. This is the first experimental study where submolecular features of single DNA molecules are observed in dry environment. The knowledge of DNA structure when dried and deposited on flat substrates is important for proper understanding of DNA’s electronic behavior and its eventual nanotechnology applications.

Error Size of the Helix (screw) Groove by Grinding

This paper presents further results in addressing this issue and builds upon the results obtained within the project GACR No. 101/07/0751 (research was supported by Czech Grant Agency), and the findings and information obtained from grant project GACR No. 101/05/2562. The problems are oriented to the production and sharpening of rotary tools, especially because all the know-how is owned by foreign companies. The main chapter is devoted to "Solution of the dependance of undercutting of the helical grooves on the grinding wheel diameter, its thickness and depth of the cut" at zero thickness of the grinding wheel. This method is an original analytical method for calculating the undercutting and is a part of the theoretical studies of the grinding helix slot. Then follows a passage, which defines the actual width of the spiral groove profiles at various grinding wheels. The present article summarizes only part of a broad range of problems in the area.

Precision Machining of Ceramics Plunger Matching Parts with Double Helix Groove

In order to improve the performance of the engine oil pump, a growing number of engine designers are employing ceramic plunger matching parts instead of metal plunger matching parts due to its excellent properties. We compared the stress and deformation change of the metal and ceramic couplings by Finite Element Method (FEM), and the advantages of ceramic plunger matching parts were validated in this paper. After determining the machining technology of plunger and sleeve, the machining processes of difficult-machining positions such as inlet and outlet oil holes, spiral grooves and so on, were analyzed in detail. The results of measurement and test show that the ceramic plunger matching parts are fully suitable for the design and work requirements.

Hydration sites of unpaired RNA bases: a statistical analysis of the PDB structures

BackgroundHydration is crucial for RNA structure and function. X-ray crystallography is the most commonly used method to determine RNA structures and hydration and, therefore, statistical surveys are based on crystallographic results, the number of which is quickly increasing.ResultsA statistical analysis of the water molecule distribution in high-resolution X-ray structures of unpaired RNA nucleotides showed that: different bases have the same penchant to be surrounded by water molecules; clusters of water molecules indicate possible hydration sites, which, in some cases, match those of the major and minor grooves of RNA and DNA double helices; complex hydrogen bond networks characterize the solvation of the nucleotides, resulting in a significant rigidity of the base and its surrounding water molecules. Interestingly, the hydration sites around unpaired RNA bases do not match, in general, the positions that are occupied by the second nucleotide when the base-pair is formed.ConclusionsThe hydration sites around unpaired RNA bases were found. They do not replicate the atom positions of complementary bases in the Watson-Crick pairs.

Predicting RNA-binding sites from the protein structure based on electrostatics, evolution and geometry

An RNA-binding protein places a surface helix, β-ribbon, or loop in an RNA helix groove and/or uses a cavity to accommodate unstacked bases. Hence, our strategy for predicting RNA-binding residues is based on detecting a surface patch and a disparate cleft. These were generated and scored according to the gas-phase electrostatic energy change upon mutating each residue to Asp−/Glu− and each residue's relative conservation. The method requires as input the protein structure and sufficient homologous sequences to define each residue's relative conservation. It yields as output a priority list of surface patch residues followed by a backup list of surface cleft residues distant from the patch residues for experimental testing of RNA binding. Among the 69 structurally non-homologous proteins tested, 81% possess a RNA-binding site with at least 70% of the maximum number of true positives in randomly generated patches of the same size as the predicted site; only two proteins did not contain any true RNA-binding residues in both predicted regions. Regardless of the protein conformational changes upon RNA-binding, the prediction accuracies based on the RNA-free/bound protein structures were found to be comparable and their binding sites overlapped as long as there are no disordered RNA-binding regions in the free structure that are ordered in the corresponding RNA-bound protein structure.