Alpha-helical Research Articles

Sequence of the SARS-CoV-2 Spike Transmembrane Domain Encodes Conformational Dynamics.

The homotrimeric SARS-CoV-2 spike protein enables viral infection by undergoing a large conformational transition, which facilitates the fusion of the viral envelope with the host cell membrane. The spike protein is anchored to the SARS-CoV-2 envelope by its transmembrane domain (TMD), composed of three TM helices, each contributed by one of the protomers of spike. Although the TMD is known to be important for viral fusion, whether it is a passive anchor of the spike or actively promotes fusion remains unknown. Specifically, it is unclear if the TMD and its dynamics facilitate the prefusion to postfusion conformational transition of the spike. Here, we computationally study the dynamics and self-assembly of the SARS-CoV-2 spike TMD in homogeneous POPC and cholesterol containing membranes. Atomistic simulations of a long TM helix-containing protomer segment show that the membrane-embedded segment bobs, tilts and gains and loses helicity, locally thinning the membrane. Coarse-grained multimerization simulations using representative TM helix structures from the atomistic simulations exhibit diverse trimer populations whose architecture depends on the structure of the TM helix protomer. While a symmetric conformation reflects the symmetry of the resting spike, an asymmetric TMD conformation could promote membrane fusion through the stabilization of a fusion intermediate. Together, our simulations demonstrate that the sequence and length of the SARS-CoV-2 spike TM segment make it inherently dynamic, that trimerization does not abrogate these dynamics and that the various observed TMD conformations may enable viral fusion.

Effects of rolling on eating quality, starch structure, and water distribution in cooked indica rice dough.

Given the composition of rice and its lack of gluten proteins, rice flour fails to form a cohesive and elastic dough when mixed directly with water. Consequently, many rice products rely on rice sheets (RS) made by rolling cooked rice dough. Limited research exists on how the rolling process impacts the properties and structure of cooked indica rice dough. This study investigated the effect of the number of rolling passes on the eating quality, starch structure, and water distribution of cooked fermented indica RS formed by dough. When the number of rolling passes reached six, the RS (RP-6) that was obtained exhibited the lowest cooking loss, the highest hardness, adhesiveness, and chewiness, and optimal stretchability. It also demonstrated the lowest water loss after freezing. Dense microstructures were observed on both the surface and cross-section of RP-6. More ordered starch crystal structures and double helix structures were formed. The relative peak area of tightly bound water significantly increased in RP-6, indicating a stronger bonding status between the starch and water molecules. However, excessive rolling passes (more than six) led to a partial disruption of the internal RS structure, resulting in a decline in eating quality. The study demonstrated the importance of the rolling process in improving the performance of RS. It was found that a moderate number of rolling passes was conducive to producing excellent RS, providing a theoretical basis for the production of high-quality rice-based products such as rice noodles, dumplings, and cakes. © 2024 Society of Chemical Industry.

Topological structure, rheological characteristics and biological activities of exopolysaccharides produced by Saccharomyces cerevisiae ADT

Saccharomyces cerevisiae ADT is an edible fungus, with limited research on its exopolysaccharides (EPS). Three types of exopolysaccharides (EPS60, EPS80, and EPS100) were obtained through multiple purification steps using varying concentrations of ethanol in this study. The topological structure, rheological properties, and biological characteristics of EPS were investigated. High performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) analyses indicated that the three EPS are primarily made up of mannose with a small amount of glucose. Acetyl groups were also found, along with the presence of α-type pyranose and β-type pyranose. The Congo Red test and X-ray diffraction results reflected the absence of a triple helix structure and crystal properties. Atomic force microscopy (AFM) revealed the self-assembly of three exopolysaccharides into various topological structures under different concentration gradients, and a clear network structure of entangled chains was observed. EPS60, EPS80 and EPS100 displayed pseudoplasticity, weak gel behavior and thermal stability. Significantly, EPS exhibited antioxidant activity in a dose-dependent manner and showed no acute cytotoxicity to RAW264.7 and HEK293T cells. Therefore, EPS in this study is anticipated to be utilized in natural antioxidants, medications, and functional materials.

Ultrasonic‐assisted Extraction, Structural Characteristics and Activity of Polysaccharides from Gymnocladus Chinensis Baill.

In this study, the response surface method (RSM) was used to determine the optimal parameters of ultrasonic assisted extraction of Gymnocladus chinensis Baill. polysaccharides (GCBP). The optimal extraction conditions were as follows: a liquid‐solid ratio of 50.4 mL/g, an extraction temperature of 60 °C, an extraction time of 43 min, and an extraction power of 240 W. Under these conditions, the extraction rate of GCBP reached 50.1%. Three fractions of GCBP‐40, GCBP‐60 and GCBP‐80 with sugar contents of 64.33%, 59.16% and 59.46% were obtained by different concentrations of ethanol purification. All the three fractions were consisted of six monosaccharides with different ratio, namely Man, Rha, Gal, Glu, Ara and Xyl. From Congo red test, it is confirmed that all three fractions could have a triple helix structure. In addition, the antioxidant and hypoglycemic experiments showed that all three components had excellent antioxidant activity (DPPH free‐radical scavenging activity, ABTS free‐radical scavenging activity, and OH‐ free‐radical scavenging activity) and hypoglycemic activity (α‐glucosidase inhibitory activity).

Cryo-EM structure of single-layered nucleoprotein-RNA complex from Marburg virus

Marburg virus (MARV) causes lethal hemorrhagic fever in humans, posing a threat to global health. We determined by cryogenic electron microscopy (cryo-EM) the MARV helical ribonucleoprotein (RNP) complex structure in single-layered conformation, which differs from the previously reported structure of a double-layered helix. Our findings illuminate novel RNP interactions and expand knowledge on MARV genome packaging and nucleocapsid assembly, both processes representing attractive targets for the development of antiviral therapeutics against MARV disease.

A Multifunctional DNA Nanoassembly for Cancer Cell Detection and Combined Gene-Chemotherapy Therapy.

Although DNAzyme is a promising gene therapy agent, low cellular uptake efficiency, poor biological stability, and the unsatisfactory effect of monotherapy limit its development. Herein, a multifunctional DNA nanoassembly (RCA product-aptamer-DNAzyme, RAD) was constructed for cancer cell detection and targeted delivery of doxorubicin (DOX) and DNAzyme. Briefly, the rolling circle amplification (RCA) product was employed as a scaffold, and each repeated sequence was designed to combine with three single-stranded DNA (ssDNA), which carried the aptamer AS1411 sequence, fluorescent group, and DNAzyme sequence, respectively. Up to 40 groups of ssDNA can be assembled into an RCA product, resulting in a high affinity for cancer cells and stronger fluorescent signals. Due to the high binding affinity, RAD displayed high sensitivity for the detection of HepG-2 cells (the limit of detection was 200 cells/mL). In addition, with the formation of the double helix structure, each RAD could load up to 200 DOX molecules. Subsequently, RAD could efficiently and selectively deliver DOX and DNAzyme into cancer cells through the multivalent interaction between the aptamers and membrane nucleolin. Then, the released DNAzyme could recognize and cleave survivin mRNA under the action of Mg2+, leading to the apoptosis of HepG-2 cells for gene therapy, while DOX inserted into intracellular DNA to inhibit cell proliferation, realizing chemotherapy. According to the results, RAD-DOX displayed enhanced therapeutic effects compared with individual gene therapy or chemotherapy, and RAD could protect membrane nucleolin-negative cells from the effects of DOX. Overall, given the enhanced serum stability, high drug-loading capacity, and excellent selective cellular uptake ability of RAD, this strategy shows great potential in the field of cancer therapy.

γ-irradiation of wheat flour dough: The influence of starch hierarchical structure and physicochemical properties

Irradiation has been shown to cause a change in physicochemical properties and starch depolymerization of wheat flour. However, the impact of starch hierarchical structure and physicochemical properties on dough's viscoelastic behavior during irradiation treatment remains unexplored. Therefore, this study investigated the effect of γ-irradiation (0, 5, 10, 15, and 20 kGy) on the viscoelastic properties of dough and the hierarchical structure and physicochemical characteristics of starches isolated from irradiated dough. Irradiation weakened the gluten network structure and decreased the starch-gluten interaction. Moreover, irradiation reduced the dough's elasticity, viscosity, deformation-resistant capacity, hardness, springiness, cohesiveness, and resilience. Irradiation treatment disrupted the short-range ordered structure, reduced the crystalline lamellae thickness and crystallinity, and dissociated the double helix structure of starch, thus increasing solubility and decreasing peak, trough, and final viscosities. Correlation analysis revealed that the lamellar structure, crystalline structure, short-range ordered structure, and pasting viscosities of starch were the key factors affecting the dough's viscoelastic properties during irradiation treatment.

Investigating the efficacy of uncrosslinked porcine collagen coated vascular grafts for neointima formation and endothelialization.

This study evaluates the efficacy of uncrosslinked porcine collagen coated vascular grafts (UPCCVG) in facilitating neointima formation and endothelialization. Prior to coating, the uncrosslinked porcine collagen underwent comprehensive characterization employing SDS-PAGE, image analysis, circular dichroism and immunogenicity. The PET substrate of the vascular graft was coated with collagen solution utilizing the dip-coating method. Water permeability, blood leakage resistance, radial compliance, hemolysis, cytotoxicity and cell proliferation of UPCCVG in vitro were studied. Subsequent in vivo evaluation involved the implantation of UPCCVG as a substitute for the porcine abdominal aorta. Digital subtraction angiography (DSA) was employed to evaluate UPCCVG patency post-implantation, while histology, immunohistochemistry, and scanning electron microscopy were utilized to assess neointima formation and endothelialization. The in vivo thrombosis of UPCCVG was analyzed simultaneously to further characterize its blood compatibility. The uncrosslinked collagen demonstrated high purity, maintaining its triple helix structure and molecular weight akin to the type I bovine collagen standard substrate, indicative of preserved biological activity and low immunogenicity. UPCCVG exhibited water permeability, blood leakage resistance, radial compliance and blood compatibility comparable to commercial grafts. DSA revealed satisfactory patency of UPCCVG without evidence of stenosis or swelling at the 3-week post-implantation mark. Histological analysis illustrated well-developed neointima with appropriate thickness and controlled proliferation. Immunohistochemistry confirmed the presence of endothelial cells (VWF positive) and smooth muscle cells (α-SMA positive) within the neointima, indicating successful endothelialization. Moreover, the morphology of the neointima surface closely resembled that of the natural artery tunica intima, oriented along the direction of blood flow. UPCCVG, composed of uncrosslinked porcine collagen, demonstrates promising potential in fostering neointima formation and endothelialization while mitigating intimal hyperplasia. This biocompatible uncrosslinked porcine collagen merits further investigation for its clinical applications in vascular reconstruction.

Study on the Structural Changes of Boneless Chicken Claw Collagen and Its Effect on Water Retention Performance.

The purpose of this study was to explore the water retention mechanism of chicken claws by detecting the structural changes in collagen in boneless chicken claws under different expansion rates. Firstly, boneless chicken claw collagen with different expansion rates (0%, 10%, 20%, 30%, 40%, 50%) was extracted by the acid-enzyme complex method, and the changes in collagen were determined by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), low-field nuclear magnetic resonance LF-NMR) and surface hydrophobicity to explore the mechanism that leads to changes in the water retention performance. The results of scanning electron microscopy showed that with the increase in the expansion rate, collagen molecules showed curling, shrinking, breaking and crosslinking, forming a loose and irregular pore-like denatured collagen structure. UV analysis showed that the maximum absorption wavelength of chicken claw collagen was blue shifted under different expansion rates, and the maximum absorption peak intensity increased first and then decreased with the increase in expansion rate. The FTIR results showed that collagen had obvious characteristic absorption peaks in the amide A, B, I, II and III regions under different expansion rates, and that the intensity and position of the characteristic absorption peaks changed with the expansion rate. The results of the CD analysis showed that collagen at different expansion rates had obvious positive absorption peaks at 222 nm, and that the position of negative absorption peaks was red shifted with the increase in expansion rate. This shows that the expansion treatment makes the collagen of chicken claw partially denatured, and that the triple helix structure becomes relaxed or unwound, which provides more space for the combination of water molecules, thus enhancing the water absorption capacity of boneless chicken claw. The results of the surface hydrophobicity test showed that the surface hydrophobicity of boneless chicken claw collagen increased with the increase in expansion rate and reached the maximum at a 30% expansion rate, and then decreased with the further increase in the expansion rate. The results of LF-NMR showed that the water content of boneless chicken claws increased significantly after the expansion treatment, and that the water retention performance of chicken claws was further enhanced with the increase in the expansion rate. In this study, boneless chicken claws were used as raw materials, and the expansion process of boneless chicken claws was optimized by acid combined with a water-retaining agent, which improved the expansion rate of boneless chicken claws and the quality of boneless chicken claws. The effects of the swelling degree on the collagen structure, water absorption and water retention properties of boneless chicken claws were revealed by structural characterization. These findings explain the changes in the water retention of boneless chicken claws after expansion. By optimizing the expansion treatment process, the water retention performance and market added value of chicken feet products can be significantly improved, which is of great economic significance.

3D-printed multifunctional chiral metamaterial with invariant sound absorption under large deformation and low-frequency vibration control

ABSTRACT Acoustic metamaterials provide a distinctive route for reducing low-frequency noise and vibration; however, most are characterised by their singular functionality, e.g. sound absorption or vibration suppression. We present a 3D-printed multifunctional chiral metamaterial (MCM) with double helix structures inspired by cochlea and DNA for excellent acoustic, mechanical, vibration isolation and mitigation properties. By employing impedance matching, nearly perfect sound absorption can be obtained and kept invariably in the low-frequency range under strain from +25% to −25%, as confirmed by the standard impedance tube tests. The double helix structure provides versatile mechanical properties, including compressibility, stretchability, and recoverability. Excellent vibration isolation ability from 94 Hz and strong elastic wave attenuation performance between 199 and 254 Hz based on bandgap strategy are demonstrated by isolation and mitigation vibration tests and simulations. This 3D printed structure presents a promising solution for multipath noise control, setting a paradigm for biologically inspired multifunctional materials.

Optimizing prolyl hydroxylation for functional recombinant collagen in Escherichia coli

Collagen, a key extracellular matrix component, is renowned for its biocompatibility, biodegradability, and bioactivity, finding wide applications in food, medicine, cosmetics, and industry. Recombinant collagen expression in Escherichia coli offers advantages such as shorter production cycles and lower costs compared to extraction from animal tissues, though it is known to lack essential post-translational modifications, such as proline hydroxylation, which are crucial for its stability and biological function. Studies have shown that certain prolyl hydroxylases, including BaP4H, DsP4H, and L593, exhibit relatively high modification efficiency in the E. coli expression system. However, structures and functions of recombinant human type III collagen after modification by three prolyl hydroxylases remain uncertain. In this study, we investigated the percentage of proline hydroxylation, hydroxylation sites, circular dichroism spectra, and biological functions of recombinant human type III collagen modified by various prolyl hydroxylases. The results indicated that the L593 exhibited the highest percentage of proline hydroxylation, and the percentage of proline hydroxylation was closely associated with the formation of the collagen triple helix, while the hydroxylation ratio of prolines is not positively correlated with the stability of the collagen triple helix structure. The biological function results showed that the cell adhesion of recombinant collagen 3-3(BaP4H) and 3-3(L593) was significantly enhanced, which was closely related to the triple helix structure of recombinant human type III collagen. Our study provides valuable insights into the industrial production and biological applications of collagen, enhancing its functional research and scalability.

Molecular dynamics simulation: Effect of sulfation on the structure of curdlan triple helix in aqueous solution

In this work, by using molecular dynamics simulations, we elucidate the effect of sulfation substitution on the stability of the curdlan triple helix structure. The simulation results indicate that the stability of the triple helix structure is significantly influenced by the sites of sulfation substitution. The substitution at the O2 site directly disrupts the hydrogen bonding network between the triple helix chains, significantly destroying the triple helix conformation. When substitutions occur at both the O4 and O6 sites simultaneously (O4,6), the electrostatic repulsion between numerous sulfate groups introduces considerable energy perturbation to the triple helix, leading to alterations in the glucan chain conformation and consequent destabilization of the triple helix structure. Meanwhile, we find that even if the sulfation substitution is performed at the same substitution sites, the difference in the degree of substitution also has an impact on the triple helix stability. The resistance of the triple helix to sulfation substitution at O2 is weak, and low degree of substitution can lead to the unwinding of the triple helix. However, it demonstrates higher resistance to substitution at O4,6 where only higher degree of substitution results in triple helix destabilization.

Optimization of Extraction Process, Structure Characterization, and Immunomodulatory Activity of Polysaccharides from Black Garlic

AbstractUltrasound assisted extraction (UAE) was used to extract polysaccharides from black garlic, and the extraction process for UAE of black garlic polysaccharides (BGPs) was optimized via RSM coupled with genetic algorithm. The optimal extraction process parameters were obtained as follows: extraction time of 30 min, liquid‐to‐solid ratio of 29 mL/g, extraction temperature of 51 ℃, and ultrasound power of 418 W, and the yield of BGPs was 10.17% ± 0.14%. Subsequently, the crude BGPs were further purified by DEAE‐52 cellulose and Sephadex G‐100 to obtain a homogeneous fraction (BGPs‐1‐SG with the molecular weight of 1.37 × 106 Da) that was comprised of mannose (Man), glucuronic acid (GlcA), rhamnose (Rha), glucose (Glc), and fucose (Fuc) with a molar ratio of 40.23:71.06:2.96:85.38:7.32. Congo red and circular dichroism spectroscopy indicate that BGPs‐1‐SG has a triple helix structure. Scanning electron microscope and atomic force microscope demonstrate that BGPs‐1‐SG showed irregular structures including sheet‐like, rod‐shaped, irregular spherical structures, and aggregated in aqueous solutions. Moreover, BGPs‐1‐SG could increase viability, phagocytic rate, and NO content of RAW264.7 cells. Furthermore, BGPs‐1‐SG could promote the secretion and mRNA expression levels of IL‐1β, IL‐6, and TNF‐α. The findings can provide an important reference for the development of functional foods.

Characterization of Exopolysaccharides from Lactiplantibacillus plantarum PC715 and Their Antibiofilm Activity Against Hafnia alvei.

Exopolysaccharides (EPSs) secreted by lactic acid bacteria have the potential to enhance human health by showing various biological functions. This study investigated the biological role and antibiofilm properties of EPS715, a new neutral EPS produced by pickled vegetables originating from Lactobacillus plantarum PC715. The results indicate that EPS715 is primarily composed of rhamnose, glucose, and mannose. Its molecular weight (Mw) is 47.87 kDa, containing an α-glucoside linkage and an α-pyranose ring. It showed an amorphous morphology without a triple helix structure. Furthermore, EPS715 showed improved antioxidant activity. Specifically, its scavenging capacity of ABTS+ radicals, DPPH radicals, and the hydroxyl (·OH) reduction capacity at 5 mg/mL was 98.64 ± 2.70%, 97.37 ± 0.79%, and 1.64 ± 0.05%, respectively. Its maximal scavenging capacity was >40%, and the hydroxyl (·OH) radical scavenging ability was dose-dependent. Moreover, the biofilm of various pathogens including S. aureus, B. cereus, S. saprophyticus, Acinetobacter spp., and H. alvei was substantially dispersed and affected by EPS715, with a maximum inhibition rate of 78.17% for H. alvei. The possible mechanism by which EPS715 shows antibiofilm properties against the H. alvei may be attributed to its effects on the auto-aggregation, hydrophilic characteristics, and motility of Hafnia spp. Thus, EPS715 has significant antioxidant and antibiofilm characteristics that may hold substantial potential for applications in food and medicinal products.

Comparison of polysaccharides from stem barks and flowers of Magnolia officinalis: Compositional characterization, hypoglycemic and photoprotection activities.

The extraction of polysaccharides from stem barks and flowers of Magnolia officinalis were optimized using response surface methodology and the maximum yields were 4.12 ± 0.06 % and 5.5 ± 0.08 %, respectively. Three homogeneous polysaccharides including MOBP-I, MOBP-II and MOFP-I were further purified and their compositional characterization were compared. Molecular weights of MOBP-I, MOBP-II and MOFP-I were 5.9 × 103, 6.8 × 103 and 3.9 × 104 Da, respectively. Gas chromatography (GC) analysis suggested that MOBP-I, MOBP-II and MOFP-I were composed of rhamnose, arabinose, mannose, glucose and galactose at different ratios and exhibited different appearance and glycosidic linkages. MOFP-I but not MOBP-I and MOBP-II had three helix structures. MOBP-I, MOBP-II and MOFP-I showed significant hypoglycemic and photoprotection capacities with different efficacy. MOBP-I had greater hypoglycemic activity, as evidenced by the increased α-glucosidase inhibition activity and glucose consumption in insulin-resistant HepG2 cells. MOBP-II and MOFP-I were more powerful in reversing ultraviolet-B (UVB)-irradiated photoaging of HaCaT cells. The difference of polysaccharides compositions might explain for their bioactivity discrepancy.

The synergistic enhancement or inhibition of different molecular weight components of mannoproteins after ultrafiltration on the encapsulation.

This study investigated the effects of molecular weight regulation on mannoproteins (MPs) in encapsulating both monomeric and oligomeric proanthocyanidins (MOPC). To achieve this, two different conformations of MPs were fractionated by ultrafiltration into two main molecular weight components. The results indicated that regulating molecular weight through ultrafiltration altered the conformation of MPs chains, which in turn affected the intermolecular forces with MOPC. Specifically, the interactions among the different molecular weight components of MPs formed a cross-linking network. High molecular weight components provided external support to this network, while low molecular weight components contributed to internal stabilization. The dense, flexible, and irregular coil structure of MPs facilitated the entry of MOPC into the internal spaces of the cross-linking network. Additionally, protein unfolding into a more stable β-sheet structure further stabilized MPs' cross-linking network, enhancing its capacity to encapsulate MOPC. The presence of more hydrophobic regions and positive charges within the proteins increased the number of binding sites for MOPC. This study aimed to identify the primary structural forms of MPs with potent initial bitter inhibition capabilities on MOPC, and a proposed ultrafiltration method was introduced to modify the triple helix structure of polysaccharide, offering a foundational theoretical framework for enhancing the functional attributes of current or prospective MPs. Additionally, the mixed regulation of polysaccharides with varying conformations was also beneficial for guiding the production of high-efficiency polysaccharide products.

Insight into characteristics in rice starch under heat- moisture treatment: Focus on the structure of amylose/amylopectin

Heat-moisture treatment (HMT) could improve the structure and physicochemical characteristics of rice starch, the structural changes of amylose and amylopectin needed to be further investigated. Hence, the starch, amylose and amylopectin were modified by HMT with different moisture contents (MC). As MC increased, starch granules became irregular, amylose appeared molten while amylopectin was less damaged. The crystal structure of starch was disrupted by HMT. The increase in the double helix structure of amylose exhibited more drastic tendency towards molecular rearrangement than amylopectin did. In addition, the reduced proportion of amylopectin A chain could affect the rearrangement of amylose. The solubility and pasting temperature improved, but the enthalpy decreased. Moderate MC (20 %, 25 %) could enhance the viscosity and dynamic viscoelasticity. HMT promoted the conversion of RDS to RS, which was significantly increased by 85.26 % at HMT-40 %. These findings contributed to a better understanding of the mechanisms by which HMT affected starch.

Commercial Space Industry Development from the Perspective of the Triple Helix: Evidence from China and the United States

Abstract: The university-industry-government triple helix has been an ideal approach to interpret the growth of innovative industries, especially in the context of todays technological leap. This study examines the commercial space sectors in United States and China, the two leading space powers, to analyze how the triple helix structures evolve and synergize to shape their respective industries. It is found that in the United States, the helix is rooted in legislation and procurement support, spurred by a well-developed industrial system, and reinforced by extensive enterprise-university collaboration programs. In contrast, the Chinese triple helix formation trajectory begins with experimental policies and space infrastructure construction, evolves through enterprises considered positioning in reusable rocket and satellite internet, and is potentially propelled by an expanding scale of talents exiting state-owned space institutions or fostered by emerging academies. After that, a lateral comparison between the two triple-helix models is undertaken to unveil the characteristics, similarities, and disparities within the commercial space industries of these two nations. This paper concludes that, for nations aiming at establishing a commercially sustainable space industry, the essence lies in a fully developed triple helix where efforts of government, industry, and academia can systematically converge without significant lag in any aspect. The paper also mentions the potential benefits of commercial space cooperation between the United States and China.

Designing novel multiepitope mRNA vaccine targeting Hendra virus (HeV): An integrative approach utilizing immunoinformatics, reverse vaccinology, and molecular dynamics simulation.

Human and animal health is threatened by Hendra virus (HeV), which has few treatments. This in-silico vaccine design study focuses on HeV G (glycoprotein), F (fusion protein), and M (matrix protein). These proteins were computationally assessed for B and T-cell epitopes after considering HeV strain conservation, immunogenicity, and antigenicity. To improve vaccination immunogenicity, these epitopes were selectively ligated into a multiepitope construct. To improve vaccination longevity and immunological response, adjuvants and linkers were ligated. G, F, and M epitopes were used to create an mRNA HeV vaccine. Cytotoxic, helper, and linear B-lymphocytes' epitopes are targeted by this vaccine. The population coverage analysis demonstrates that multi-epitope vaccination covers 91.81 percent of CTL and 98.55 percent of HTL epitopes worldwide. GRAVY evaluated the vaccine's well-characterized physicochemical properties -0.503, indicating solubility and functional stability. Structure analysis showed well-stabilized 2° and 3° structures in the vaccine, with alpha helix, beta sheet, and coil structures (Ramachandran score of 88.5% and Z score of -3.44). There was a strong affinity as shown by docking tests with TLR-4 (central score of -1139.4 KJ/mol) and TLR-2 (center score of -1277.9 KJ/mol). The coupled V-apo, V-TLR2, and V-TLR4 complexes were tested for binding using molecular dynamics simulation where extremely stable complexes were found. The predicted mRNA structures provided significant stability. Codon optimization for Escherichia. coli synthesis allowed the vaccine to attain a GC content of 46.83% and a CAI score of 1.0, which supports its significant expression. Immunological simulations indicated vaccine-induced innate and adaptive immune reactions. Finally, this potential HeV vaccine needs more studies to prove its efficacy and safety.

Investigating the effect of water on collagen triple helix stability

Collagen provides essential structural support to diverse body tissues through its unique triple helix structure. Collagen stability is crucial for proper tissue function and any disruptions in its stability can lead to various health issues. Prior research has identified multiple factors affecting collagen stability. However, despite its fundamental presence in biological systems, the influence of water remains inadequately explored. Here, we performed molecular dynamics simulations on collagen model peptides (CMPs) with varying experimental stability profiles to investigate the influence of water on collagen stability. Our simulations revealed variations in both the hydrogen bonding (H-bonding) patterns between the CMPs and surrounding water molecules, as well as the water networks formed around CMPs. We noted that water molecules form H-bonds with collagen residues which enhance its structural stability. Additionally, water molecules assemble around the collagen and form topological water networks (TWNs) through intermolecular H-bonding. These TWNs further stabilizes the collagen structure. Overall, this research provides insight into the role of water molecules in preserving the stability of the collagen triple helix.