Conformational Structure Research Articles

Design, development and testing of 3D-printed conformal energy absorbing structures

Landing a spacecraft on a foreign body is a key challenge to explore new worlds. Besides the task of approach and decent the landing has to nullify the residual kinetic energy. For large or medium-sized landers this will be done by the landing gear with shock absorbers inside the landing legs. For small landers alternative ways of reducing the shocks of the touchdown have to be developed, since the landing gear has a higher mass fraction when the lander gets smaller.A suitable method for protecting a lander from the shock of impact is a crushable shell, which absorbs the kinetic energy at touchdown by plastic deformation of its core material.The core material is commonly made of aluminum honeycomb which is very lightweight and has a constant energy dissipation characteristic. On the other hand, the materials stiffness strongly relates to the direction of load, since tilted load transfers reduce the energy absorptivity drastically. This applies specially for landers with no active guidance and control ability. In those cases, the entire vehicle has to be covered with crushable elements with the honeycomb cells aligned accordingly.A new and innovative method of omni-directional crash protection is a metal grid which can be manufactured additively. With this feature the lander can land in any inclination without losing crush performance.In this paper the development of a 3D-printed energy absorbing structure is presented. Hardware tests have shown the effectiveness of this method in comparison to the benchmark of honeycomb shock absorbers.

A rapid procedure to generate stably transfected HEK293 suspension cells for recombinant protein manufacturing: Yield improvements, bioreactor production and downstream processing

The human cell line HEK293 is one of the preferred choices for manufacturing therapeutic proteins and viral vectors for human applications. Despite its increased use, it is still considered in disadvantage in production aspects compared to cell lines such as the CHO cell line. We provide here a simple workflow for the rapid generation of stably transfected HEK293 cells expressing an engineered variant of the SARS-CoV-2 Receptor Binding Domain (RBD) carrying a coupling domain for linkage to VLPs through a bacterial transpeptidase-sortase (SrtA). To generate stable suspension cells expressing the RBD-SrtA, a single two plasmids transfection was performed, with hygromycin selection. The suspension HEK293 were grown in adherent conditions, with 20% FBS supplementation. These transfection conditions increased cell survival, allowing the selection of stable cell pools, which was otherwise not possible with standard procedures in suspension. Six pools were isolated, expanded and successfully re-adapted to suspension with a gradual increase of serum-free media and agitation. The complete process lasted four weeks. Stable expression with viability over 98% was verified for over two months in culture, with cell passages every 4–5 days. With process intensification, RBD-SrtA yields reached 6.4 μg/mL and 13.4 μg/mL in fed-batch and perfusion-like cultures, respectively. RBD-SrtA was further produced in fed-batch stirred tank 1L-bioreactors, reaching 10-fold higher yields than perfusion flasks. The trimeric antigen displayed the conformational structure and functionality expected. This work provides a series of steps for stable cell pool development using suspension HEK293 cells aimed at the scalable production of recombinant proteins.

New Hypothesis Insight of Structural Properties on Four Tau Peptide Fragments in Alzheimer's Disease: Origin from the Histidine Behaviors.

During protein folding and misfolding, structural properties and aggregation tendency can be significantly influenced by histidine behaviors (tautomeric behaviors and protonation behaviors). The original reasons were derived from the net charge changes and the various N/N-H orientation on imidazole rings. In the current study, total 18 independent REMD simulations were performed to investigate the histidine behaviors on four Tau peptide fragments (MBD, including R1, R2, R3, and R4 fragments). We found that, compared to R1, R2, R3 except (εδ), and R4 systems with flexible structural features, only R3(εδ) has dominating conformational structure (possibility of 81.3%) with three β-strand structures in parallel β-sheet structures at I4-K6and I24-H26, as well as antiparallel β-sheet structure at G19-L21. Importantly, the H25 and H26 residues (in R3(εδ) system) are directly involved in the sheet structure formations and strong H-bonded interactions (possibility range of 31.3%-44.7%). Furthermore, the donors and acceptors analysis confirmed that only R3(εδ) shows faraway amino acids interaction features in both H25 and H26 residues, and such cooperation effects of two histidine residues contribute to current structural features. The current study will be helpful to further enrichment of the histidine behavior hypothesis, it provides new insight for understanding protein folding and misfolding.

Identification of Potential TMPRSS2 Inhibitors for COVID-19 Treatment in Chinese Medicine by Computational Approaches and Surface Plasmon Resonance Technology.

Coronavirus disease-19 (COVID-19) pneumonia continues to spread in the entire globe with limited medication available. In this study, the active compounds in Chinese medicine (CM) recipes targeting the transmembrane serine protease 2 (TMPRSS2) protein for the treatment of COVID-19 were explored. The conformational structure of TMPRSS2 protein (TMPS2) was built through homology modeling. A training set covering TMPS2 inhibitors and decoy molecules was docked to TMPS2, and their docking poses were re-scored with scoring schemes. A receiver operating characteristic (ROC) curve was applied to select the best scoring function. Virtual screening of the candidate compounds (CCDs) in the six highly effective CM recipes against TMPS2 was conducted based on the validated docking protocol. The potential CCDs after docking were subject to molecular dynamics (MD) simulations and surface plasmon resonance (SPR) experiment. A training set of 65 molecules were docked with modeled TMPS2 and LigScore2 with the highest area under the curve, AUC, value (0.886) after ROC analysis selected to best differentiate inhibitors from decoys. A total of 421 CCDs in the six recipes were successfully docked into TMPS2, and the top 16 CCDs with LigScore2 higher than the cutoff (4.995) were screened out. MD simulations revealed a stable binding between these CCDs and TMPS2 due to the negative binding free energy. Lastly, SPR experiments validated the direct combination of narirutin, saikosaponin B1, and rutin with TMPS2. Specific active compounds including narirutin, saikosaponin B1, and rutin in CM recipes potentially target and inhibit TMPS2, probably exerting a therapeutic effect on COVID-19.

Near-infrared Piezochromic Materials at High Pressure.

The study of piezochromic materials (PCMs) has become an attractive field and numerous scholars have reported various material structures and phenomena. PCMs incorporating near-infrared (NIR) emission have led to a broader range of applications due to the strong penetration and interference resistance of longer wavelength light sources. However, NIR PCMs are still rare due to difficulties in tuning molecular configuration, conformation and stacking structure. In this review, organic compounds are classified according to their types and structures, and recent advances in NIR PCMs are comprehensively summarized and described. The various factors affecting the piezochromic properties from the perspective of the compound structure are shown. The effects of pressure on the photophysical changes of different compounds are discussed. It is expected to provide ideas for subsequent NIR PCMs, from structural design to predicting their photophysical properties under pressure.

Magnetic field-assisted cascade effects of improving the quality of gels-based meat products: A mechanism from myofibrillar protein gelation

Physics-assisted processing technologies have huge potential in the meat processing industry. By modeling two essential procedures (pickling and preheating) of gels-based meat products, this work investigated the cascade effects of a new physical technology (magnetic field) on the conformational structures and gel properties of myofibrillar proteins (MPs). Samples were subjected with four magnetic field (MF)-assisted treatments (group A, both processes without MF; group B, pickling without MF combining with preheating with 4.5 mT MF; group C, pickling with 3.0 mT MF combining with preheating without MF; group D, pickling with 3.0 mT MF combining with preheating with 4.5 mT MF). The result showed that MF-assisted treatments significantly improved water holding capacity (WHC) of MP gels compared with group A (46.9%), reaching the maximum value of 52.1% in group D.According to the low-field nuclear magnetic results, group D decreased the percentages of P22 (6.97%) and increased the percentages of P21 (93%), which showed that water molecules were more tightly bound to each other. Meanwhile, the unfolding of α-helix and the formation of random coil of MF-assisted treatments resulted in more exposure of internal groups, leading to the formation of a dense network. These findings would provide new insights to improve the quality of gels-based meat products via the MF.

Molecular simulation studies on a zwitterionic peptide-dendrimer conjugate for integrin αvβ3 binding.

Zwitterionic dendrimer is an effective carrier, which can restore the natural conformation of peptide segments for high bioaffinity by a hydrogen bond-induced conformational constraint approach. However, it is still unknown whether the approach is applicable for the dendrimers with different geometric sizes. Therefore, the characteristics of conjugates made from zwitterionic poly(amidoamine) (PAM) and the arginine-glycine-aspartic acid (RGD) peptide were examined to elucidate the effects of the geometric sizes of the PAM dendrimer on the conformational structure and stability of the peptide. The results show that the RGD fragments had almost the same structure and stability when conjugated with PAM(G3, G4, or G5) dendrimers. However, when conjugated with PAM(G1 or G2) dendrimers, the structural stability of these fragments was found to be much worse. Also, the structure and stability of RGD segments conjugated with PAM(G3, G4, or G5) were not affected when additional EK segments were inserted. Moreover, we observed that RGD fragments conjugated with PAM(G3, G4, or G5) dendrimers were structurally stable and similar when the concentration of NaCl was 0.15 and 0.5M. Furthermore, we show that PAM(G3, G4, or G5)-RGD conjugates bind strongly to integrin αvβ3.

Controlling the assembly of soy β-conglycinin to fabricate heat-stable particles for high protein liquid systems.

Recently, there is a growing interest in developing protein-fortified liquid systems, which are formulated to provide special nutrient combinations to those with special dietary needs. The fabrication of heat-stable protein for protein-fortified liquid systems relies heavily on precise control of the edible protein-building process. Results suggested that heat-stable 7S protein particles (7SPPs) could be obtained by preheating at 100 °C for an extended time, whereas 7S proteins with better gelling properties were discovered after preheating at lower temperatures. According to the findings of the protein conformational and morphological characterization, the 7SPPs showed rather stable tertiary and secondary structures as well as size distributions, which might be responsible for their heat stability. Additionally, during the reheating test, suspensions of 7SPPs showed no signs of gelation and had a low viscosity even though the protein content was as high as 120 mg mL-1 . However, 7S proteins with improved gelling properties were found to show rising aggregate size, higher susceptibility and larger conformational structure changing rates upon reheating treatment. Soy β-conglycinin (7S) proteins with tunable heat stability were successfully prepared by preheating 10 mg mL-1 protein dispersions at various temperatures (80-120 °C) and durations (15-120 min). These findings provide fundamental insights for developing 7S-based protein-fortified systems. © 2023 Society of Chemical Industry.

Flexible electromagnetic wave absorption material: Multiscale synergistic approach to achieve whole X-band absorption and thermal stealth property

Fabric-based electromagnetic wave (EMW) absorption materials are desirable owing to their inherent flexibility, cost-effectiveness, and easily conformable lightweight structures. However, the problems such as high density and susceptibility to abrasion limit their applications and service life. Herein, flexible fabric-based EMW absorption material (FEMWAM) were prepared by a multiscale synergistic approach. At the microscopic scale, CF@NiCo2O4@MnO2 absorbents with enhanced impedance matching and interfacial polarization are prepared by solvent method and hydrothermal process. The influence of heterostructure on the electromagnetic response is also examined. At the macroscopic scale, flexible FEMWAM are prepared by freeze-drying. The electromagnetic parameters of FEMWAM was effectively regulated by altering the amount of the CF@NiCo2O4@MnO2 absorbents, which achieve excellent EMW absorption performance and thermal insulation property while maintaining flexibility. The minimal reflection loss (RLmin) of −27.8 dB can be achieved at a thickness of 2.70 mm, and an EAB covering the complete X-band can be obtained when the thickness is in the range of 3.20–3.26 mm. The large thickness range provides convenience for the control of dimensional accuracy in actual production, so as to better adapt to practical applications. These findings provide effective guidance for the preparation of EMW absorption materials with excellent flexibility, thermal insulation properties and absorption performance.

Exploiting conformational dynamics to modulate the function of designed proteins

With the recent success in calculating protein structures from amino acid sequences using artificial intelligence-based algorithms, an important next step is to decipher how dynamics is encoded by the primary protein sequence so as to better predict function. Such dynamics information is critical for protein design, where strategies could then focus not only on sequences that fold into particular structures that perform a given task, but would also include low-lying excited protein states that could influence the function of the designed protein. Herein, we illustrate the importance of dynamics in modulating the function of C34, a designed α/β protein that captures β-strands of target ligands and is a member of a family of proteins designed to sequester β-strands and β hairpins of aggregation-prone molecules that lead to a variety of pathologies. Using a strategy to "see" regions of apo C34 that are invisible to NMR spectroscopy as a result of pervasive conformational exchange, as well as a mutagenesis approach whereby C34 molecules are stabilized into a single conformer, we determine the structures of the predominant conformations that are sampled by C34 and show that these attenuate the affinity for cognate peptide. Subsequently, the observed motion is exploited to develop an allosterically regulated peptide binder whose binding affinity can be controlled through the addition of a second molecule. Our study emphasizes the unique role that NMR can play in directing the design process and in the construction of new molecules with more complex functionality.

Manifolds without real projective or flat conformal structures

In any dimension at least five we construct examples of closed smooth manifolds with the following properties: (1) they have neither real projective nor flat conformal structures; (2) their fundamental group is a non-elementary Gromov hyperbolic group. These examples are obtained via relative strict hyperbolization.

Detailing Protein-Bound Uremic Toxin Interaction Mechanisms with Human Serum Albumin in the Pursuit of Designing Competitive Binders.

Chronic kidney disease is the gradual progression of kidney dysfunction and involves numerous co-morbidities, one of the leading causes of mortality. One of the primary complications of kidney dysfunction is the accumulation of toxins in the bloodstream, particularly protein-bound uremic toxins (PBUTs), which have a high affinity for plasma proteins. The buildup of PBUTs in the blood reduces the effectiveness of conventional treatments, such as hemodialysis. Moreover, PBUTs can bind to blood plasma proteins, such as human serum albumin, alter their conformational structure, block binding sites for other valuable endogenous or exogenous substances, and exacerbate the co-existing medical conditions associated with kidney disease. The inadequacy of hemodialysis in clearing PBUTs underscores the significance of researching the binding mechanisms of these toxins with blood proteins, with a critical analysis of the methods used to obtain this information. Here, we gathered the available data on the binding of indoxyl sulfate, p-cresyl sulfate, indole 3-acetic acid, hippuric acid, 3-carboxyl-4-methyl-5-propyl-2-furan propanoic acid, and phenylacetic acid to human serum albumin and reviewed the common techniques used to investigate the thermodynamics and structure of the PBUT-albumin interaction. These findings can be critical in investigating molecules that can displace toxins on HSA and improve their clearance by standard dialysis or designing adsorbents with greater affinity for PBUTs than HSA.

DFT insight of hydroxide degradation pathways for heterocyclic quaternary ammonium cations in anion exchange membranes

The alkaline stability of the heterocyclic quaternary ammoniums (QAs) is crucial for the long-term operation of anion exchange membrane fuel cells (AEMFCs). Here, we calculate the degradation barriers of 21 heterocyclic QAs and analyze the degradation mechanism systematically by density functional theory (DFT). We have found that the chair conformation and ring structure of heterocyclic QAs can inhibit Hoffman degradation of β-hydrogens and that methyl SN2 is the primary degradation pathway for most heterocyclic QAs. Higher ring strain and the introduction of electron-withdrawing groups are disadvantageous to the stability. The positions of substituted methyl affect the stability of the molecules significantly. Forming bicyclic structures is also an effective strategy to improve stability. Among tethering strategies of anion exchange membranes (AEMs), tethering at the 4-position is more stable than at the 1-position. The superacid-catalyzed condensation reaction is still the best AEM preparation strategy which balances the stability and synthetic difficulty. Compared with the experimental value, the average error of simulation is only 0.56 kcal mol−1. Our prediction method can also be extended to various alkali concentrations, and the results are consistent with the experiments. At low alkali concentrations, the heterocyclic QAs mainly degrade by SN2 reactions. At high alkali concentrations, the groups mainly degrade by Hofmann elimination reactions.

The marvelous dna macromolecule: computer modeling of dna 3d structure and diversity of watson-crick duplex conformations

The work reviews the development of ideas about the 3D structure of DNA and the mechanisms of its formation, from the discovery of the Double Helix to the present day. It tracks the methods of modeling the 3D structure at different stages of the study of the main molecule of life. The discussion underscores a marvelous expedient in DNA molecular structure and its adaptability to important biological functions based on the results of calculations of the intra- and intermolecular interactions of macromolecule subunits. The work presents new data about substantial contribution of chemically monotonous and conformationally flexible sugarphosphate backbone to the formation of sequence-dependent 3D structure of DNA. The diversity of the conformational possibilities of DNA is visible both in the formation of duplexes (as well as triplexes and quadruplexes) with different geometric parameters for base pairs and in the formation of duplexes with Watson-Crick nucleoside pairs containing local conformations corresponding to different regions of the torsion angles of the sugar-phosphate backbone (different conformational classes). Based on our calculations, these classes can be divided into two groups. The first group includes local conformations in which the torsion angles are close to one of energy minima of its isolated elemental repeating fragment, and the second group consists of conformations with one or more of these angles deviating from that of the nearest energy minimum by more than 30°. The regularities of the formation of the local 3D structure of these two groups differ significantly.

Effects of isochoric freezing on myofibrillar protein conformational structures of chicken breasts

This study investigated the myofibrillar protein conformational structures during the isochoric freezing of chicken breasts at three different temperatures of −4, −8, and −12 °C. Experiments conducted using 2.5% NaCl solution revealed that samples treated at −4 °C (25 MPa) showed no significant (P > 0.05) effect in the myofibrillar protein structure, while those treated at −8 °C (60 MPa) showed significant changes (P < 0.05) in protein properties including dityrosine, solubility, and sulfhydryl, suggesting the partial recovery of the samples. However, samples treated at −12 °C (85 MPa) indicated complete destruction of the myofibrillar protein structure. Results of the myofibrillar sarcomeres evaluation further verified that freezing at −4 °C was able to maintain chicken breast meat protein structure. Insights on the possibilities of preserving meat under isochoric freezing in the food industry are envisaged to be gained from the current study.

Poly(ethylene) oxide/erbium oxide as T2 and T1-T2 dual-mode MRI diagnostic nanofibres

A novel magnetic resonance imaging (MRI) diagnostic nanofibres were synthesised using Er2O3 nanoparticles (2% to 8%) embedded in the PEO matrix via electrospinning. The prepared PEO/Er2O3 nanofibres were fully characterised, and the magnetic relaxivity study for MRI contrast enhancement was evaluated. The findings showed that the fibre diameter became broader with increasing nanofiller loading. The encapsulation of Er2O3 nanoparticles in PEO fibres demonstrated excellent entrapment efficiency using the electrospinning method. The reduction of the crystallinity index provoked changes in the crystallite size, thus contributing to the amorphous component. The addition of Er2O3 nanoparticles in the PEO matrix demonstrated the changes in the conformational structure of the peak intensity, shape and position of the C–O–C stretching absorptions. PEO/Er2O3 nanofibres have successfully demonstrated potential T2 and T1-T2 dual-mode diagnostic nanofibres in MRI 1.5 T. Therefore, it is considered a great achievement in the detection sensitivity for cancer diagnosis due to its potential diagnostic use that can be activated in two-way.

Studies on the inhibition of α-glucosidase by biflavonoids and their interaction mechanisms

Biflavonoids are a kind of polyphenol compounds with numerous biological functions. However, the potential inhibitory activities of biflavonoids on α-glucosidase are yet unknown. Here, the inhibitory effects of two biflavonoids (amentoflavone and hinokiflavone) on α-glucosidase and their interaction mechanisms were explored using multispectral approaches and molecular docking. The results showed that the inhibitory activities of biflavonoids were much better compared with monoflavonoid (apigenin) and acarbose, and the order of inhibition ability was hinokiflavone > amentoflavone > apigenin > acarbose. These flavonoids were noncompetitive inhibitors of α-glucosidase and showed synergistic inhibition effects with acarbose. Additionally, they could statically quench the intrinsic fluorescence of α-glucosidase, and form the non-covalent complexes with enzyme primarily through hydrogen bonds and van der Waals forces. The binding of flavonoids changed the conformational structure of α-glucosidase, therefore impairing the enzyme activity. The findings suggested that biflavonoids could be considered as potential hypoglycemic functional foods in diabetes therapy.

Intrinsic mechanisms for the inhibition effect of graphene oxide on the catalysis activity of alpha amylase

Comprehending the interactions between graphene oxide (GO) and enzymes is critical for understanding the toxicities of GO. In this study, the inherent interactions of GO with α-amylase as a typical enzyme, and the impacts of GO on the conformation and biological activities of α-amylase were systematically investigated. The results reveal that GO formed ground-state complex with α-amylase primarily via hydrogen bonding and van der Waals interactions, thus quenching the intrinsic fluorescence of the protein statically. Particularly, the strong interactions altered the microenvironment of tyrosine and tryptophan residues, caused rearrangement of polypeptide structure, and reduced the contents of α-helices and β-sheets, thus changing the conformational structure of α-amylase. According to molecular docking results, GO binds with the amino acid residues (i.e., His299, Asp300, and His305) of α-amylase mainly through hydrogen bonding, which is in accordance with in vitro incubation experiments. As a consequence, the ability of α-amylase to catalyze starch hydrolysis into glucose was depressed by GO, suggesting that GO might cause dysfunction of α-amylase. This study discloses the intrinsic binding mechanisms of GO with α-amylase and provides novel insights into the adverse effects of GO as it enters organisms.

Asynchronous piezochromic fluorescence and phosphorescence behavior observed in an organic dual emission crystal

Mechanochromic luminescence (MCL) is attracting much attention due to its promising applications and academic importance. However, the present studies mainly focus on fluorescent dyes, and investigations on organic phosphorescent materials are still lack. In the current work, a new organic room temperature phosphorescence‒fluorescence dual emission crystal with well-separated emission peaks is used to investigate the MCL behaviors by the diamond anvil cell technique in conjunction with the spectroscopic measurements. The results demonstrate the remarkably asynchronous piezochromic fluorescence and phosphorescence behavior in both emission colors and intensities. The theoretical analyses and calculations indicate that the high pressure induced molecular conformation and stacking structure changes can differently influence the energy levels and distributions of singlet and triplet excited states, which is responsible for the interesting photo-physical properties. This work provides a new perspective of understanding the effect of molecular confined environments on organic light emitting properties.

Molecular Dynamics Simulation of the Conformational Structure of Polyampholyte Polypeptides at the Surface of a Charged Gold Nanoparticle in External Electric Field

Molecular Dynamics Simulation of the Conformational Structure of Polyampholyte Polypeptides at the Surface of a Charged Gold Nanoparticle in External Electric Field