Helical Parameters Research Articles

Continuous Casting Preparation Process of Helical Fiber-Reinforced Metal Matrix Composites

To improve the strength of the metal while maintaining good plasticity, helical fibers are added to the metal matrix. How to form helical fiber and control its parameters in the preparation process are urgent problems to be solved in the study of helical fiber-reinforced metal matrix composites. In this paper, the continuous casting process of helical fiber-reinforced metal matrix composites was proposed. To reduce the difficulty of the experiment, the formation process of helical fiber on metal matrix and the relationship between the continuous casting process parameters and helical shape fiber parameters were studied by preparing helical carbon fiber-reinforced lead matrix composites with a low-melting-point metal matrix. The results show that this process can produce helical fiber-reinforced metal matrix composite stably and continuously, and the helical shape parameters of the composite can be controlled by changing the process parameters of continuous casting. To further improve the practical application of this process, helical carbon fiber-reinforced aluminum matrix composites were prepared. The test result in terms of mechanical property shows that the tensile strength and elongation of the composite were improved. This indicates that the reinforced phase of the helical structure of the metal matrix composite has higher strength and toughness compared with the matrix metal.

Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes.

Mixed double helices formed by RNA and DNA strands, commonly referred to as hybrid duplexes or hybrids, are essential in biological processes like transcription and reverse transcription. They are also important for their applications in CRISPR gene editing and nanotechnology. Yet, despite their significance, the hybrid duplexes have been seldom modeled by atomistic molecular dynamics methodology, and there is no benchmark study systematically assessing the force-field performance. Here, we present an extensive benchmark study of polypurine tract (PPT) and Dickerson-Drew dodecamer hybrid duplexes using contemporary and commonly utilized pairwise additive and polarizable nucleic acid force fields. Our findings indicate that none of the available force-field choices accurately reproduces all the characteristic structural details of the hybrid duplexes. The AMBER force fields are unable to populate the C3'-endo (north) pucker of the DNA strand and underestimate inclination. The CHARMM force field accurately describes the C3'-endo pucker and inclination but shows base pair instability. The polarizable force fields struggle with accurately reproducing the helical parameters. Some force-field combinations even demonstrate a discernible conflict between the RNA and DNA parameters. In this work, we offer a candid assessment of the force-field performance for mixed DNA/RNA duplexes. We provide guidance on selecting utilizable force-field combinations and also highlight potential pitfalls and best practices for obtaining optimal performance.

Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein containing both a kinase and a GTPase, are a leading cause of the familial form of PD. Pathogenic LRRK2 mutations increase LRRK2 kinase activity. While the bulk of LRRK2 is found in the cytosol, the protein associates with membranes where its Rab GTPase substrates are found, and under certain conditions, with microtubules. Integrative structural studies using single-particle cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) have revealed the architecture of microtubule-associated LRRK2 filaments, and that formation of these filaments requires LRRK2's kinase to be in the active-like conformation. However, whether LRRK2 can interact with and form filaments on microtubules in its autoinhibited state, where the kinase domain is in the inactive conformation and the N-terminal LRR domain covers the kinase active site, was not known. Using cryo-ET, we show that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules. While these filaments are stabilized by the same interfaces seen in the active-LRRK2 filaments, we observed a new interface involving the N-terminal repeats that were disordered in the active-LRRK2 filaments. The helical parameters of the autoinhibited-LRRK2 filaments are different from those reported for the active-LRRK2 filaments. Finally, the autoinhibited-LRRK2 filaments are shorter and less regular, suggesting they are less stable.

On the effect of flux-surface shaping on trapped-electron modes in quasi-helically symmetric stellarators

Using a novel optimization procedure, it has been shown that the Helically Symmetric eXperiment stellarator can be optimized for reduced trapped-electron-mode (TEM) instability [Gerard et al., Nucl. Fusion 63, (2023) 056004]. Presently, with a set of 563 experimental candidate configurations, gyrokinetic simulations are performed to investigate the efficacy of available energy EA, quasi-helical symmetry, and flux-surface shaping parameters as metrics for TEM stabilization. It is found that lower values of EA correlate with reduced growth rates, but only when separate flux-surface shaping regimes are considered. Moreover, configurations with improved quasi-helical symmetry demonstrate a similar reduction in growth rates and less scatter compared to EA. Regarding flux-surface shaping, a set of helical shaping parameters is introduced that show increased elongation is strongly correlated with reduced TEM growth rates, however, only when the quasi-helical symmetry is preserved. Using a newly derived velocity-space-averaged TEM resonance operator, these trends are analyzed to provide insights into the physical mechanism of the observed stabilization. For elongation, stabilization is attributed to geometric effects that reduce the destabilizing particle drifts across the magnetic field. Regarding quasi-helical symmetry, the TEM resonance in the maximally resonant trapping well is shown to increase as the quasi-helical symmetry is broken, and breaking quasi-helical symmetry increases the prevalence of highly resonant trapping wells. While these results demonstrate the limitations of using any single metric as a linear TEM proxy, it is shown that quasi-helical symmetry and plasma elongation are highly effective metrics for reducing TEM growth rates in helical equilibria.

Dynamics analysis of helical gear considering de-meshing and reverse impact with EHL lubrication condition.

The purpose of this paper was to study the evolution and dynamic characteristics of the helical gear system co-existence response considering the occurrence of de-meshing and reverse impact under lubrication conditions. The double-three tooth alternate meshing model of a helical gear was established, and the time-varying geometric parameters, motion parameters, and load distribution of positive meshing and reverse impact were analyzed, respectively. The variation of oil film parameters and the coupling between oil film stiffness and meshing stiffness of a gear system were studied according to the equivalent lubrication model of a helical gear. Considering the phenomenon that the meshing state changed from positive meshing to de-meshing and reverse impact, the dynamics model was established. The global bifurcation diagram, the attraction domain, the phase portrait, and the Poincaré section were used to analyze the evolution of a coexistence response and dynamic characteristics with helical gear system parameters.

Circular and Linear Dichroism for the Analysis of Small Noncoding RNA Properties.

Useful structural information about the conformation of nucleic acids can be quickly acquired by circular and linear dichroism (CD/LD) spectroscopy. These techniques, rely on the differentialabsorption of polarised light andare indeed extremely sensitive to subtle changes in the structure of chiralbiomolecules. Many CD analyses of DNA or DNA:protein complexes have beenconducted with substantial data acquisitions. Conversely, CDRNA analysisare still scarce, despite the fact that RNA plays a wide cellular function. This chapter seeks to introduce the reader to the use of circular, lineardichroism and in particular the use of Synchrotron Radiation for such samples. The use of these techniques on small noncoding RNA (sRNA) will be exemplified by analyzing changes in base stacking and/or helical parameters for the understanding of sRNA structure and function, especially by translating the dynamics of RNA:RNA annealing but also to access RNA stability or RNA:RNA alignment. The effect of RNA remodeling proteins will also be addressed. These analyses are especially useful to decipher the mechanisms by which sRNA will adopt the proper conformation thanks to the action of proteins such as Hfq or ProQ in the regulation of the expression of their target mRNAs.

Research on measurement method of drilling fluid rheological parameters based on helical pipe

Monitoring drilling fluid rheological parameters can provide a basis for assessing downhole complexities and analyzing well control risks. Among various methods for measuring drilling fluid rheological parameters, the pipe flow method allows for real-time online measurements. However, it faces limitations due to the long length of pipes and challenges in miniaturization. Based on a survey of domestic and international research, this study conducted numerical simulations to analyze the differences in flow pressure drop of drilling fluid between helical pipes and straight pipes. It clarified the impact of helical pipe structural parameters, drilling fluid process parameters, and rheological parameters on drilling fluid flow pressure drop. Utilizing the constitutive equations of Bingham, power-law, and Herschel-Bulkley fluids, a regression model was established to convert the flow pressure drop of drilling fluid between helical pipes and straight pipes. The reliability of the numerical simulation results was verified using a self-developed drilling fluid flow pressure measurement device, which yielded an average relative error of only 2.13%. These research findings provide a theoretical basis for the development of drilling fluid rheological parameter monitoring devices based on helical pipes and the corresponding software.

Helical Three Dimensional Reconstruction Using Bayesian Optimization for Cryogenic Electron Microscopy.

Three-dimensional (3D) reconstruction for cryogenic electron microscopy (cryo-EM) often falls into an ill-posed problem owing to several uncertainties in observations, including noise. To reduce excessive degree of freedom and avoid overfitting, the structural symmetry is often used as a powerful constraint. In the case of the helix, the entire 3D structure is determined by the subunit 3D structure and two helical parameters. There is no analytical method to simultaneously obtain both of the subunit structure and helical parameters. A common approach is to employ an iterative reconstruction in which the two optimizations are performed alternately. However, iterative reconstruction does not necessarily converge when a heuristic objective function is used for each optimization step. Also, the obtained 3D reconstruction highly depends on the initial guess of the 3D structure and the helical parameters. Herein, we propose a method for estimating the 3D structure and helical parameters that also performs an iterative optimization; however, the objective function for each step is derived from a single objective function to make the algorithm convergent and less sensitive to the initial guess. Finally, we evaluated the effectiveness of the proposed method by testing it on cryo-EM images, which were challenging to reconstruct using conventional methods.

Modeling of a two-degree-of-freedom fiber-reinforced soft pneumatic actuator

AbstractFiber winding reinforcement is widely used in soft robotic manipulators actuated by pressurized fluids. However, the specific effect of each type of winding on the bending motion of a tubular soft robotics manipulator with three chambers has not been explored widely. We present the development of precise finite element (FE) simulations and investigate the effect of helical fiber winding parameters on the bending motion of a two-degree-of-freedom manipulator with three internal chambers. We first show the development of an FE simulation that optimizes convergence and computational time and precisely matches the behavior of soft robots in practice. Compared to single-chamber robots, simulating three-chamber designs is more challenging due to the complex geometry. We then apply our FE model to simulate all the parameter variations. We show that for helical winding with a constant pitch, the closer the center of a chamber is to the intersection of the windings, the lower the bending stiffness of the chamber is. To minimize bending stiffness variation in different bending directions, the optimal angle between the center of the first chamber and the intersection of the two helical windings are 0° and 12°. Reducing the pitch of the helical windings or using other types of windings (i.e., ring winding or six helical winding) reduces the stiffness variation across different bending directions. The FE simulations are compared with experiments showing that the model can capture complex bending behaviors of the manipulator, even though the estimation tends to be less accurate at higher bending angles.

Visualization and Parametric Study on Vortex Shedding Suppression of Cylindrical Structures in Offshore Engineering Using Large Eddy Simulation

Cylindrical structures are widely used in offshore and marine engineering, but they may suffer from vortex-induced vibration under the influence of ocean or wave currents, which can lead to severe fatigue damage. In this study, we applied the open-source software Open-Source Field Operation and Manipulation (OpenFOAM) to investigate the characteristics of fluid flow around offshore cylindrical structures, taking into account the effect of helical strake parameters, such as pitch and strake number. The aim of this study is to explore the possibility of suppressing vortex shedding with different helical strake parameters. Numerical simulation results demonstrated that attaching a helical strake to the bare cylinder destroyed vortex shedding in offshore cylindrical structures. The vortex visualization showed that the helical strake destroyed the three-dimensional vortex structures. Moreover, the lift coefficient data showed that the vibration frequency of the cylinder decreased after attaching the helical strake, indicating that the vortex-induced vibrations on the wake flow tended to fade. The results suggest that the helical strake is a promising option for suppressing the wake vortex shedding of cylindrical structures in offshore engineering.

Delta SARS-CoV-2 s2m Structure, Dynamics, and Entropy: Consequences of the G15U Mutation.

Bioinformatic analysis of the Delta SARS-CoV-2 genome reveals a single nucleotide mutation (G15U) in the stem-loop II motif (s2m) relative to ancestral SARS-CoV-2. Despite sequence similarity, unexpected differences between SARS-CoV-2 and Delta SARS-CoV-2 s2m homodimerization experiments require the discovery of unknown structural and thermodynamic changes necessary to rationalize the data. Using our reported SARS-CoV-2 s2m model, we induced the G15U substitution and performed 3.5 microseconds of unbiased molecular dynamics simulation at 283 and 310 K. The resultant Delta s2m adopted a secondary structure consistent with our reported NMR data, resulting in significant deviations in the tertiary structure and dynamics from our SARS-CoV-2 s2m model. First, we find differences in the overall three-dimensional structure, where the characteristic 90° L-shaped kink of the SARS-CoV-2 s2m did not form in the Delta s2m resulting in a "linear" hairpin with limited bending dynamics. Delta s2m helical parameters are calculated to align closely with A-form RNA, effectively eliminating a hinge point to form the L-shape kink by correcting an upper stem defect in SARS-CoV-2 induced by a noncanonical and dynamic G:A base pair. Ultimately, the shape difference rationalizes the migration differences in reported electrophoresis experiments. Second, increased fluctuation of the Delta s2m palindromic sequence, within the terminal loop, compared to SARS-CoV-2 s2m results in an estimated increase of entropy of 6.8 kcal/mol at 310 K relative to the SARS-CoV-2 s2m. The entropic difference offers a unique perspective on why the Delta s2m homodimerizes less spontaneously, forming fewer kissing dimers and extended duplexes compared to SARS-CoV-2. In this work, both the L-shape reduction and palindromic entropic penalty provides an explanation of our reported in vitro electrophoresis homodimerization results. Ultimately, the structural, dynamical, and entropic differences between the SARS-CoV-2 s2m and Delta s2m serve to establish a foundation for future studies of the s2m function in the viral lifecycle.

X-ray Structure Characterization of the Selective Recognition of AT Base Pair Sequences.

The rational design of small molecules that target specific DNA sequences is a promising strategy to modulate gene expression. This report focuses on a diamidinobenzimidazole compound, whose selective binding to the minor groove of AT DNA sequences holds broad significance in the molecular recognition of AT-rich human promoter sequences. The objective of this study is to provide a more detailed and systematized understanding, at an atomic level, of the molecular recognition mechanism of different AT-specific sequences by a rationally designed minor groove binder. The specialized method of X-ray crystallography was utilized to investigate how the sequence-dependent recognition properties in general, A-tract, and alternating AT sequences affect the binding of diamidinobenzimidazole in the DNA minor groove. While general and A-tract AT sequences give a narrower minor groove, the alternating AT sequences intrinsically have a wider minor groove which typically constricts upon binding. A strong and direct hydrogen bond between the N-H of the benzimidazole and an H-bond acceptor atom in the minor groove is essential for DNA recognition in all sequences described. In addition, the diamidine compound specifically utilizes an interfacial water molecule for its DNA binding. DNA complexes of AATT and AAAAAA recognition sites show that the diamidine compound can bind in two possible orientations with a preference for water-assisted hydrogen bonding at either cationic end. The complex structures of AAATTT, ATAT, ATATAT, and AAAA are bound in a singular orientation. Analysis of the helical parameters shows a minor groove expansion of about 1 Å across all the nonalternating DNA complexes. The results from this systematic approach will convey a greater understanding of the specific recognition of a diverse array of AT-rich sequences by small molecules and more insight into the design of small molecules with enhanced specificity to AT and mixed DNA sequences.

Cryo-EM structure of the flight muscle thick filament from the bumble bee, Bombus ignitus, with novel non-myosin densities revealed.

The cryo-EM structure of the flight muscle thick filament of Bombus ignitus (order Hymenoptera) has been resolved at 6 Å resolution. By the comparison with similar asynchronous flight muscle thick filament structures from Lethocerus (Diptera) and Lethocerus (Hemiptera), all three present highly consistent backbone structure with very similar tail structure and have closely similar helical parameters. The myosin heads in Bombus are disordered like those of Drosophila; both insects have higher wingbeat frequencies than Lethocerus where the myosin heads are ordered. The three filament structures differ mostly in their non-myosin proteins and make the interpretation of densities corresponding to flightin and myofilin uncertain. However, using Alphafold model prediction, multiple sequence alignment and mass spectrometry, a more complete profile of flightin and myofilin has been determined. The full length of that portion of flightin within the thick filament annulus of Bombus threads its way through two myosin curved layers, contacts three other myosin curved layers and has a close contact with the Skip 3 region. The previously-identified, highly-conserved WYR domain of Bombus flightin contacts three myosin tails. With assistance from Alphafold, an atomic model was built for Bombus flightin from residue 41 to residue 151 (C-terminus). The other non-myosin protein, myofilin is more diverse in sequence, length and shape among the three reconstructed filaments, although it also shows a highly conserved density and sequence at its N-terminus, which we have named the “LKG domain”. Both flightin and myofilin have close contact with the paramyosin core, these three non-myosin proteins are believed to work together to determine and stabilize the thick filament structure. Supported by NIH/NIGMS.

Crystal structures of 'ALternative Isoinformational ENgineered' DNA in B-form.

The first structural model of duplex DNA reported in 1953 by Watson & Crick presented the double helix in B-form, the form that genomic DNA exists in much of the time. Thus, artificial DNA seeking to mimic the properties of natural DNA should also be able to adopt B-form. Using a host-guest system in which Moloney murine leukemia virus reverse transcriptase serves as the host and DNA as the guests, we determined high-resolution crystal structures of three complexes including 5'-CTTBPPBBSSZZSAAG, 5'-CTTSSPBZPSZBBAAG and 5'-CTTZZPBSBSZPPAAG with 10 consecutive unnatural nucleobase pairs in B-form within self-complementary 16 bp duplex oligonucleotides. We refer to this ALternative Isoinformational ENgineered (ALIEN) genetic system containing two nucleobase pairs (P:Z, pairing 2-amino-imidazo-[1,2-a]-1,3,5-triazin-(8H)-4-one with 6-amino-5-nitro-(1H)-pyridin-2-one, and B:S, 6-amino-4-hydroxy-5-(1H)-purin-2-one with 3-methyl-6-amino-pyrimidin-2-one) as ALIEN DNA. We characterized both position- and sequence-specific helical, nucleobase pair and dinucleotide step parameters of P:Z and B:S pairs in the context of B-form DNA. We conclude that ALIEN DNA exhibits structural features that vary with sequence. Further, Z can participate in alternative stacking modes within a similar sequence context as captured in two different structures. This finding suggests that ALIEN DNA may have a larger repertoire of B-form structures than natural DNA. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.

Improved technology of frequency-selective UHF electromagnetic shields containing helical elements

An improved technology of frequency-selective electromagnetic shields has been considered. The technology has been improved by embedding classic Archimedean helical elements made from foiled materials into the bulk of the shields for the improvement of the frequency-selective performance of the shields and pinning of these elements in the bulk of the shields by means of fusion bonding. These design features provide for the main advantage of the improved technology in comparison with counterparts, i.e., lower time consumption. The technology has been improved in the following two aspects: 1) identification of helical element parameters providing for the greatest energy loss of the UHF electromagnetic radiation interacting with the helical elements; 2) identification of the optimum helical element arrangement in the shield bulk providing for the smallest transmission and reflection coefficient of the UHF electromagnetic radiation by the shields. Technology improvement in accordance with the former of the above aspects has been achieved based on analysis of publications dealing with mathematical simulation and study of the parameters of UHF electromagnetic radiation transmission by planar helical antennas. Technology improvement in accordance with the latter aspect has been achieved based on experimental data. Test shields have been fabricated with specifically arranged embedded helical elements, and comparison has been made between the UHF electromagnetic radiation transmission and reflection coefficients of the shields. Shields fabricated in accordance with the improved technology suggested herein show good promise for the electromagnetic noise protection of electronic devices.

Chirality-Dependent and Intrinsic Auxeticity for Single-Walled Carbon Nanotubes.

Single-walled carbon nanotubes (SWCNTs) have superior mechanical properties which originate from a strong C-C covalent bond and unique nanostructure. Chirality, one of the helical structural parameters of SWCNTs, leads to differences in mechanical performance. In this work, molecular dynamics (MD) simulation was performed to analyze engineering Poisson's ratio (EPR) and incremental Poisson's ratio (IPR) of SWCNTs with different chiral angles, respectively, under tensile and compressive load, as well as the chiral effect on rigidity. We reported the minimum EPR for (4, 1) SWCNT and obtained the distribution and trend of EPR which is dependent on chiral index m. In addition, a new observation showed two exactly opposite trends of EPR existing not only in tension and compression but also in the longitudinal and radial directions. Furthermore, we found that the critical strain, over which SWCNT would be auxetic, ranged from 6% to 18% and was also chirality-dependent. Three representative SWCNTs with chiral angle of 0° (zigzag), 10.89° (chiral), and 30° (armchair) were selected for the mechanism study of auxeticity. Finally, a method of the contribution to radial strain for two main deformation modes proposed in this paper could well explain the negative IPR phenomenon.

A rolled-up-based fabrication method of 3D helical microrobots.

While the potential of using helical microrobots for biomedical applications, such as cargo transport, drug delivery, and micromanipulation, had been demonstrated, the viability to use them for practical applications is hindered by the cost, speed, and repeatability of current fabrication techniques. Hence, this paper introduces a simple, low-cost, high-throughput manufacturing process for single nickel layer helical microrobots with consistent dimensions. Photolithography and electron-beam (e-beam) evaporation were used to fabricate 2D parallelogram patterns that were sequentially rolled up into helical microstructures through the swelling effect of a photoresist sacrificial layer. Helical parameters were controlled by adjusting the geometric parameters of parallelogram patterns. To validate the fabrication process and characterize the microrobots' mobility, we characterized the structures and surface morphology of the microrobots using a scanning electron microscope and tested their steerability using feedback control, respectively. Finally, we conducted a benchmark comparison to demonstrate that the fabrication method can produce helical microrobots with swimming properties comparable to previously reported microrobots.

The comparison of self-assembling behaviour of phenyl biphenylcarboxylate and biphenyl benzoate compounds with the different length and shape of chiral terminal chain

Our recent advances on polymer-stabilised orthoconic antiferroelectric liquid crystals (PSOAFLCs) eliminated the asymmetry of switching times in electro-optical effect based on surface stabilized OAFLCs and paved the way for their effective use in many photonic and optoelectronic devices requiring very fast switching. To fabricate new modifications of PSOAFLCs, besides bi- and tetrafunctional monomers, multicomponent AFLCs mixtures with a very low meting point, high stability of the antiferroelectric phase at lower temperatures and higher helical pitch length are desirable. Herein, a very convenient synthetic method of new AFLC compounds with a phenyl biphenylcarboxylate structure of the rigid core with different length and shape of terminal chains is reported. The resulting mesomorphic properties and helical parameters are compared with those of analogues with a biphenyl benzoate structure of the rigid core. The designed AFLC compounds clearly possess definite advantages. Specifically, they exhibit lower meting points, higher clearing points, broader temperature range of the antiferroelectric phase (SmCA*) and much longer helical pitch length, especially for analogues with the shortest achiral terminal chain, but unexpectedly lower tendency to give the direct transition between the antiferroelectric and isotropic phase. The introduction of the cycloalkyl ring at the end of the chiral terminal chain increases the melting points, flattens the temperature dependence of the helical pitch and changes the sense of the helical twist, but also enhances the ability of the direct SmCA*-Iso phase transition, regardless the type of the rigid core. The obtained results highlight a possibility of utilizing compounds with the phenyl biphenylcarboxylate structure of the rigid core, designed under this work, together with previously prepared compounds with the biphenyl benzoate rigid core to formulate multicomponent OALFC mixtures with a very low melting point and a very high helical pitch length.

Assembly of von Willebrand factor tubules with in vivo helical parameters requires A1 domain insertion

AbstractThe von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) before secretion from endothelial cells into the bloodstream. The organization of VWF in the tubules promotes formation of covalently linked VWF polymers and enables orderly secretion without polymer tangling. Recent studies have described the high-resolution structure of helical tubular cores formed in vitro by the D1D2 and D′D3 amino-terminal protein segments of VWF. Here we show that formation of tubules with the helical geometry observed for VWF in intracellular WPBs requires also the VWA1 (A1) domain. We reconstituted VWF tubules from segments containing the A1 domain and discovered it to be inserted between helical turns of the tubule, altering helical parameters and explaining the increased robustness of tubule formation when A1 is present. The conclusion from this observation is that the A1 domain has a direct role in VWF assembly, along with its known activity in hemostasis after secretion.

Visualizing "Alternative Isoinformational Engineered" DNA in A- and B-Forms at High Resolution.

A fundamental property of DNA built from four informational nucleotide units (GCAT) is its ability to adopt different helical forms within the context of the Watson-Crick pair. Well-characterized examples include A-, B-, and Z-DNA. For this study, we created an isoinformational biomimetic polymer, built (like standard DNA) from four informational "letters", but with the building blocks being artificial. This ALternative Isoinformational ENgineered (ALIEN) DNA was hypothesized to support two nucleobase pairs, the P:Z pair matching 2-amino-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one with 6-amino-3-5-nitro-1H-pyridin-2-one and the B:S pair matching 6-amino-4-hydroxy-5-1H-purin-2-one with 3-methyl-6-amino-pyrimidin-2-one. We report two structures of ALIEN DNA duplexes at 1.2 Å resolution and a third at 1.65 Å. All of these are built from a single self-complementary sequence (5'-CTSZZPBSBSZPPBAG) that includes 12 consecutive ALIEN nucleotides. We characterized the helical, nucleobase pair, and dinucleotide step parameters of ALIEN DNA in these structures. In addition to showing that ALIEN pairs retain basic Watson-Crick pairing geometry, two of the ALIEN DNA structures are characterized as A-form DNA and one as B-form DNA. We identified parameters that map differences effecting the transition between the two helical forms; these same parameters distinguish helical forms of isoinformational natural DNA. Collectively, our analyses suggest that ALIEN DNA retains essential structural features of natural DNA, not only its information density and Watson-Crick pairing but also its ability to adopt two canonical forms.