Conformational Structure Research Articles

In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb's cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate's molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb.

Dual-Mode Arginine Assay Based on the Conformation Switch of a Ferrocene-Grafted Polypeptide.

Both controllable regulation of the conformational structure of a polypeptide and specific recognition of an amino acid are still arduous challenges. Here, a novel dual-mode (electrochemical and colorimetric) biosensor was built for arginine (Arg) recognition based on a conformation switch, utilizing controllable and synergistic self-assembly of a ferrocene-grafted hexadecapeptide (P16Fc) with gold nanoparticles (AuNPs). Benefiting from the flexibility and unique topological structure of P16Fc formed nanospheres, the assembly and disassembly can undergo a conformation transition induced by Arg through controlling the distance and number of Fc detached from the gold surface, producing on-off electrical signals. Also, they can induce aggregation and dispersion of AuNPs in solution, causing a color change. The mechanism of Arg recognition with polypeptide conformation regulation was well explored by combining microstructure characterizations with molecular mechanics calculations. The electrochemical and colorimetric assays for Arg were successfully established in sensitive and selective manner, not only obtaining a very low detection limit, but also effectively eliminating the interference from other amino acids and overcoming the limitation of AuNP aggregation. Notably, the conformational change-based assay with the peptide regulated by the target will make a powerful tool for the amino acid biosensing and health diagnosis.

Conformal and projective tractors from 2-frame bundles by the dressing field method

This paper is devoted to the study of conformal and projective structures, and especially their connections, in the language of 2-frames, or [Formula: see text]-structures of second order. While their normal Cartan connections are well-known, we use the dressing field method to obtain their local, mostly gauge invariant, connections. Lastly, we recall how to obtain the tractor bundle from conformal structures, and then show that we can define a projective tractor bundle using the same kind of construction.

Mechanisms Underlying the Effects of Chloroquine on Red Blood Cells Metabolism.

Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte membrane, inhibiting heme polymerase in malarial trophozoites. Accumulation of CQ prevents the conversion of heme to hemozoin, causing its toxic buildup, thus blocking the survival of Plasmodium parasites. Recently, it has been reported that CQ is able to exert antiviral properties, mainly against HIV and SARS-CoV-2. This renewed interest in CQ treatment has led to the development of new studies which aim to explore its side effects and long-term outcome. Our study focuses on the effects of CQ in non-parasitized red blood cells (RBCs), investigating hemoglobin (Hb) functionality, the anion exchanger 1 (AE1) or band 3 protein, caspase 3 and protein tyrosine phosphatase 1B (PTP-1B) activity, intra and extracellular ATP levels, and the oxidative state of RBCs. Interestingly, CQ influences the functionality of both Hb and AE1, the main RBC proteins, affecting the properties of Hb oxygen affinity by shifting the conformational structure of the molecule towards the R state. The influence of CQ on AE1 flux leads to a rate variation of anion exchange, which begins at a concentration of 2.5 μM and reaches its maximum effect at 20 µM. Moreover, a significant decrease in intra and extracellular ATP levels was observed in RBCs pre-treated with 10 µM CQ vs. erythrocytes under normal conditions. This effect is related to the PTP-1B activity which is reduced in RBCs incubated with CQ. Despite these metabolic alterations to RBCs caused by exposure to CQ, no signs of variations in oxidative state or caspase 3 activation were recorded. Our results highlight the antithetical effects of CQ on the functionality and metabolism of RBCs, and encourage the development of new research to better understand the multiple potentiality of the drug.

Reduced infectivity of nervous necrosis virus due to reversible adsorption of serum albumin onto surface protrusions of viral particles

Nervous necrosis virus (NNV) belonging to the genus Betanodavirus is highly lethal to a wide range of fish species. We investigated the reactivity of purified NNV particles with serum albumin and immunoglobulin G (IgG), which are major components in serum. Infectivity of NNV suspended in high-concentration fetal bovine serum (FBS) reduced to approximately 1/60 to 1/200 but that of NNV in ≤10% FBS did not decline. On washing out the FBS, NNV regained its infectivity, suggesting that NNV infectivity was reduced by reversible adsorption of some components in the serum onto the NNV particles. On replacing FBS with bovine serum albumin, NNV infectivity gradually reduced with increasing concentration of serum albumin. Furthermore, albumin adsorbed onto the NNV particles immobilized on enzyme-linked immunosorbent assay (ELISA) plate wells. However, the adsorbed serum albumin was easily washed out by the normal ELISA washing process using phosphate-buffered saline (PBS). Thus, serum albumin reversibly adsorbed onto NNV particles. However, purified rabbit IgG non-specifically adsorbed onto NNV particles regardless of whether conformational structures of NNV surface protrusions were partially or completely denatured, suggesting that IgG is adsorbed onto areas other than the surface protrusions on NNV particles. FBS did not interfere with the adsorption of IgG onto NNV particles. Considering that pocket structures at the apex of the NNV surface protrusions function as binding sites for cellular receptors, serum albumin may get adsorbed onto or near the pocket structures. This could be one of reasons for reduction in infectivity of NNV suspended in high-concentration FBS.

Unified Understanding of the Structure, Thermodynamics, and Diffusion of Single-Chain Nanoparticle Fluids.

Single-chain nanoparticles (SCNPs) are a fascinating class of soft nano-objects with promising properties and relevance to protein condensates, polymer nanocomposites, nanomedicine, bioimaging, catalysis, and drug delivery. We combine molecular dynamics simulations and equilibrium and time-dependent statistical mechanical theory to construct a unified understanding of how the internal conformational structure of SCNPs, of both a simple fractal globule-like form and more complex objects with multiple internal intermediate length scales, determines nm-scale intermolecular packing correlations, thermodynamic properties, and center-of-mass diffusion over a wide range of concentrations up to dense melts. The intermolecular pair correlations generically exhibit a distinctive deep correlation hole form due to SCNP internal connectivity structure and repulsive interparticle interactions associated with a globular-like conformation on the macromolecular scale, with concentration-dependent deviations at small separations. Unanticipated exponential-like dependences of the equation-of-state, osmotic compressibility, and center-of-mass diffusion constant on SCNP macromolecular packing fraction are theoretically predicted and confirmed via simulations. System-specific behaviors are found associated with SCNP internal structure, but overarching regularities are identified and understood based on a generalized effective globule conformation on macromolecular scales. Diffusivity slows down by 2-3 decades with increasing concentration and is understood as a consequence of a nonactivated excluded volume-driven weak-caging process associated with space-time correlated intermolecular forces experienced by the SCNP. Good agreement between the theory and simulations is established, testable predictions are made, and a quantitative comparison with viscosity measurements on a specific SCNP fluid is carried out. The basic theoretical approach can potentially be extended to treat the chemical and physical consequences of varying the structure of other classes of soft nanoparticles with distinctive internal nanoscale organization relevant in nanotechnology and nanomedicine, and the possible emergence of macromolecular kinetically arrested glasses.

Modification techno-functional properties of spirulina protein concentrates (Arthrospira Platensis) as O/W emulsifier by conjugation and electrostatic complexations

Spirulina (Arthrospira platensis) is an intriguing but underutilized protein source in the food industry. This study aims to investigate the effect of electrostatic complexation and conjugation on the techno-functional properties of the protein spirulina and its benefits as an emulsifier in oil-in-water (O/W) emulsion in order to broaden its application as food ingridients. The Spirulina protein concentrate (SPC) interacted with carrageenan via electrostatic and conjugation (Maillard reactions). The properties of the complexes and conjugates were then evaluated. The results showed that the turbidity, browning index, and thermal stability of the solution were influenced by the protein: polysaccharides ratios and pH conditions. The best conjugates (MR) were obtained at a ratio of 2:1 with a pH of 7.0 based on confirmation of the degree of glycation, browning index value, emulsion activity index (EAI) value, and emulsion stability index (ESI). The best electrostatic complexes (EI) were obtained at a ratio of 2:1 with a pH of 2. SPC-carrageenan conjugates and complexes exhibited different functional properties based on conformation structure by FTIR and thermal properties by DSC. Conjugation and Electrostatic Interaction increased the denaturation temperature of SPC, which were reflected in the emulsions stabilized by maillard reaction (MR), electrostatic interaction (EI), and simple mixed (SM) SPC-carrageenan. The emulsion stabilized by MR had smaller droplet sizes, was more evenly distributed, and had better stability towards heating than those stabilized by Native SPC, SM, and EI. This study provides valuable basic information for the development of spirulina protein as a green emulsifier and other type of novel food.

Evaluating the binding mechanism, structural changes and stability of ternary complexes formed by the interaction of folic acid with whey protein concentrate-80 and L-ascorbyl 6-palmitate

In the present study, we investigated the mechanisms associated with the stabilizing effects of whey protein concentrate-80 (WPC80) and L-ascorbyl 6-palmitate (LAP) on folic acid (FA). Multispectral techniques show that WPC80 binds to FA and LAP mainly through hydrophobic interactions, and that energy is transferred from WPC80 to FA and LAP in a nonradiative form (FA/LAP); The combination of FA/LAP resulted in a change in the conformation and secondary structure content of WPC80, an increase in the absolute zeta potential of the system, and a shift in the particle size distribution towards smaller sizes. The compound system exhibits strengthened antioxidant properties and favorable binding properties. Besides, WPC80 improves the storage stability of FA under different conditions. These results demonstrated that the ternary complex formed by FA co-binding with WPC80 and LAP is an effective way to improve the stability against of FA.

Kinematic analysis of kinases and their oncogenic mutations - Kinases and their mutation kinematic analysis.

Protein kinases are crucial cellular enzymes that facilitate the transfer of phosphates from adenosine triphosphate (ATP) to their substrates, thereby regulating numerous cellular activities. Dysfunctional kinase activity often leads to oncogenic conditions. Chosen by using structural similarity to 5UG9, we selected 79 crystal structures from the PDB and based on the position of the phenylalanine side chain in the DFG motif, we classified these 79 crystal structures into 5 group clusters. Our approach applies our kinematic flexibility analysis (KFA) to explore the flexibility of kinases in various activity states and examine the impact of the activation loop on kinase structure. KFA enables the rapid decomposition of macromolecules into different flexibility regions, allowing comprehensive analysis of conformational structures. The results reveal that the activation loop of kinases acts as a "lock" that stabilizes the active conformation of kinases by rigidifying the adjacent α-helices. Furthermore, we investigate specific kinase mutations, such as the L858R mutation commonly associated with non-small cell lung cancer, which induces increased flexibility in active-state kinases. In addition, through analyzing the hydrogen bond pattern, we examine the substructure of kinases in different states. Notably, active-state kinases exhibit a higher occurrence of α-helices compared to inactive-state kinases. This study contributes to the understanding of biomolecular conformation at a level relevant to drug development.

Effect of transglutaminase crosslinking combined with lactic fermentation on the potential allergenicity and conformational structure of soy protein.

Food allergies are a growing concern worldwide, with soy proteins being important allergens that are widely used in various food products. This study investigated the potential of transglutaminase (TGase) and lactic acid bacteria (LAB) treatments to modify the allergenicity and structural properties of soy protein isolate (SPI), aiming to develop safer soy-based food products. Treatment with TGase, LAB or their combination significantly reduced the antibody reactivity of β-conglycinin and the immunoglobulin E (IgE) binding capacity of soy protein, indicating a decrease in allergenicity. TGase treatment led to the formation of high-molecular-weight aggregates, suggesting protein crosslinking, while LAB treatment resulted in partial protein hydrolysis. These structural changes were confirmed by Fourier transform infrared spectroscopy, which showed a decrease in β-sheet content and an increase in random coil and β-turn contents. In addition, changes in intrinsic fluorescence and ultraviolet spectroscopy were also observed. The alterations in protein interaction and the reduction in free sulfhydryl groups highlighted the extensive structural modifications induced by these treatments. The synergistic application of TGase and LAB treatments effectively reduced the allergenicity of SPI through significant structural modifications. This approach not only diminished antibody reactivity of β-conglycinin and IgE binding capacity of soy protein but also altered the protein's primary, secondary and tertiary structures, suggesting a comprehensive alteration of SPI's allergenic potential. These findings provide a promising strategy for mitigating food allergy concerns and lay the foundation for future research on food-processing techniques aimed at allergen reduction. © 2024 Society of Chemical Industry.

Study on the binding interaction and stability of whey protein concentrate-80 with folic acid

The aim of this study was to evaluate the effects of whey protein concentrate-80 (WPC80) and folic acid (FA) on protein structure, functional properties, and on the stability of FA through non-covalent interactions. The effect of FA on the structure of WPC80 was analyzed by intrinsic fluorescence spectroscopy, ultraviolet absorption spectroscopy, and circular dichroism. The results showed that FA induced changes in the local conformation and secondary structure content of WPC80. Moreover, the particle size distribution of the system showed a tendency to become smaller and the absolute value of the zeta potential increased; the surface hydrophobicity and free sulfhydryl content of WPC80 decreased with the increase of the FA concentration, and the foaming and emulsifying properties gradually improved with the increase of the FA concentration. This indicates that FA combined causes changes in the functional properties of WPC80. Meanwhile, the binding capacity of FA to WPC80 gradually increased with its concentration, and the combination enhanced the storage stability of FA under different temperatures, aerobic and ultraviolet irradiation. This study will provide a theoretical basis for the application of FA-fortified foods.

Inorganic Polysulfides in Solution: Structural Properties and Conformational Isomerism.

We present a comprehensive theoretical examination of the structural properties of dianionic polysulfides [Sn]2- (n = 2-6), their conjugated monoacids [HSn]- (n = 2-6), and a selection of 1e--oxidized radical anions [Sn]•- (n = 2-4), in aqueous and dimethyl sulfoxide (DMSO) solutions. We investigated the structures and stabilities of various conformational isomers within these families of compounds by employing Quantum Mechanics-Molecular Mechanics (QM-MM) Molecular Dynamics (MD) simulations. The explicit inclusion of solvent molecules in the calculations revealed stable conformational structures that were previously unreported and might have appreciable concentrations in real systems. The interconversions between the isomeric structures proceed on the order of hundreds of picoseconds and are energetically similar to the isomerization processes in substituted cyclohexanes. We also conducted a detailed analysis of the stability of different isomers of the radical anion [S4]•- in solution. Our findings highlight the significant influence of the solvent on the isomerizations, a result that could be particularly relevant for enhancing the performance of metal-sulfur batteries.

Enhanced B-type starch granules proportion modulates starch-gluten interactions during the thermal processing of reconstituted doughs

This work investigated structure-properties changes of reconstituted wheat A/B starch doughs under different ratios during dynamic thermal processing. Results indicated that a change in spatial conformation and aggregation structure of the starch-gluten system was induced with heating (30 °C–86 °C). Moderately increased B starch ratio can effectively fill the gluten network and improve starch-protein interactions, which promotes the free sulfhydryl group oxidation and results in the formation of more glutenin macropolymer; this contributes to a higher degree of cross-linking and stability to the gluten network matrix. This improvement is enhanced as the heating temperature is increased. Notably, the B starch ratio requires to be controlled within a suitable range (≤ 75%) to avoid aggregation and accumulation on the gluten matrix triggered by its excess. This work may provide insights and optimization for clarifying the on-demand regulation strategy of A/B starch in dough processing.

The anti-self-dual deformation complex and a conjecture of Singer

Abstract Let ( M 4 , g ) (M^{4},g) be a smooth, closed, oriented anti-self-dual (ASD) four-manifold. ( M 4 , g ) (M^{4},g) is said to be unobstructed if the cokernel of the linearisation of the self-dual Weyl tensor is trivial. This condition can also be characterised as the vanishing of the second cohomology group of the ASD deformation complex, and is central to understanding the local structure of the moduli space of ASD conformal structures. It also arises in construction of ASD manifolds by twistor and gluing methods. In this article, we give conformally invariant conditions which imply an ASD manifold of positive Yamabe type is unobstructed.

Optimizing the power conversion processes in diluted donor/acceptor heterojunctions towards 19.4% efficiency all-polymer solar cells

All polymer solar cells (all-PSCs) promise mechanically-flexible and morphologically-stable organic photovoltaics and have aroused increased interests very recently. However, due to their disorderly conformation structures within the photoactive film, inefficient charge generation and carrier transport are observed which lead to inferior photovoltaic performance compared to smaller molecular acceptor-based photovoltaics. Here, by diluting PM6 with a cutting-edge polymeric acceptor PY-IT and diluting PY-IT with PM6 or D18, donor-dominating or acceptor-dominating heterojunctions were prepared. Synchrotron X-ray and multiple spectrometer techniques reveal that the diluted heterojunctions receive increased structural order, translating to enhanced carrier mobility, improved exciton diffusion length, and suppressed non-radiative recombination loss during the power conversion. As the results, the corresponding PM6+1%PY-IT/PY-IT+1%D18 and PM6+1%PY-IT/PY-IT+1%PM6 devices fabricated by layer-by-layer deposition received superior power conversion efficiency (PCE) of 19.4% and 18.8% respectively, along with enhanced operational lifetimes in air, outperforming the PCE of 17.5% in the PM6/PY-IT reference device.

Self-Assembled Hydrogel Membranes with Structurally Tunable Mechanical and Biological Properties.

Using supramolecular self-assembled nanocomposite materials made from protein and polysaccharide components is becoming more popular because of their unique properties, such as biodegradability, hierarchical structures, and tunable multifunctionality. However, the fabrication of these materials in a reproducible way remains a challenge. This study presents a new evaporation-induced self-assembly method producing layered hydrogel membranes (LHMs) using tropocollagen grafted by partially deacetylated chitin nanocrystals (CO-g-ChNCs). ChNCs help stabilize tropocollagen's helical conformation and fibrillar structure by forming a hierarchical microstructure through chemical and physical interactions. The LHMs show improved mechanical properties, cytocompatibility, and the ability to control drug release using octenidine dihydrochloride (OCT) as a drug model. Because of the high synergetic performance between CO and ChNCs, the modulus, strength, and toughness increased significantly compared to native CO. The biocompatibility of LHM was tested using the normal human dermal fibroblast (NHDF) and the human osteosarcoma cell line (Saos-2). Cytocompatibility and cell adhesion improved with the introduction of ChNCs. The extracted ChNCs are used as a reinforcing nanofiller to enhance the performance properties of tropocollagen hydrogel membranes and provide new insights into the design of novel LHMs that could be used for various medical applications, such as control of drug release in the skin and bone tissue regeneration.

Egg yolk peptide‐iron chelate: preparation, conformational structure, chelating mechanism and stability in vitro

SummaryIn this study, a method to produce iron‐chelating peptides derived from egg yolk proteins was developed and optimised. The egg yolk proteins were enzymolysed and ultrafiltered to prepare egg yolk peptide (EYP), and then the EYP was chelated with Fe to produce egg yolk peptide‐Fe (EYP‐Fe). The optimised mass ratio of peptide to iron, pH, temperature and reaction time were found at 8:1, pH 8.0, 40 °C and 30 min, respectively. The mean particle size of EYP‐Fe was 389.2 ± 2.61 nm, and the chelating ratio was 95.38 ± 1.93%. The measurements of FTIR, X‐ray photoelectron spectroscopy (XPS) and NMR showed that ferrous ions mainly combined with the amino and carboxyl of EYP to form EYP‐Fe. In vitro stability studies have shown that the iron release rate of the EYP‐Fe is maintained at around 5% under alkaline conditions, and there is no significant difference in iron release rate under conditions of 30 °C–80 °C; besides, it has a lower iron release rate (18%) in gastrointestinal digestion compared to FeSO4 (97.93%), indicating that the EYP‐Fe has good heat tolerance, alkalinity and digestion tolerance. The above results provide a scientific basis for the use of EYP‐Fe derived from egg yolk protein as a potential alternative to iron supplements.

Perilla protein isolate exhibits synergistic techno-functionality through modification via sequential dynamic high-pressure microfluidization and enzymatic hydrolysis

Modification of proteins derived from plant sources is crucial for enabling their versatile applications in the food industry. In the present study, structural and functional properties of individual treated perilla protein isolate (PPI) through dynamic high-pressure microfluidization (DHPM) and enzymatic hydrolysis (EH) was compared with their sequential (DHPM-EH) treatment. Native PPI thick, sharp-edged blocks transformed into a collapsed structure with wrinkles after sequential (DHPM-EH) treatment. The synergistic effect between DHPM and EH, during sequential (DHPM-EH) treatment caused greater reduction (91.9%) in PPI particle size as compared to DHPM (87.3%), and EH (84.5%), which enhanced PPI solubility, even at low pH. Above treatments altered the conformational structure of PPI as evident from changes in surface hydrophobicity, free –SH groups conversion into –SS bonds, ultraviolet absorption and fluorescence intensities changes, and decreased α-helix, while increased β-sheets. The sequential (DHPM-EH) treated PPI showed enhanced foaming capacity (×3.59), as well as increased thermal and colloidal stability.

A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution

Despite the widespread use of polymers as precipitation inhibitors in supersaturating drug formulations, the current understanding of their mechanisms of action is still incomplete. Specifically, the role of hydrophobic drug interactions with polymers by considering possible supramolecular conformations in aqueous dispersion is an interesting topic. Accordingly, this study investigated the tendency of polymers to create hydrophobic domains, where lipophilic compounds may nest to support drug solubilisation and supersaturation. Fluorescence spectroscopy with the environment-sensitive probe pyrene was compared with atomistic molecular dynamics simulations of the model drug fenofibrate (FENO). Subsequently, kinetic drug supersaturation and thermodynamic solubility experiments were conducted. As a result, the different polymers showed hydrophobic domain formation to a varying degree and the molecular simulations supported interpretation of fluorescence spectroscopy data. Molecular insights were gained into the conformational structure of how the polymers interacted with FENO in solution phase, which apart from nucleation and crystal growth effects, determined drug concentrations in solution. Notable was that even at the lowest polymer concentration of 0.01 %, w/v, there were polymer-specific solubilisation effects of FENO observed and the resulting reduction in apparent drug supersaturation provided relevant knowledge both from a mechanistic and practical perspective.

Monomeric Esterase: Insights into Cooperative Behavior, Hysteresis/Allokairy.

Herein, we present a novel esterase enzyme, Ade1, isolated from a metagenomic library of Amazonian dark earths soils, demonstrating its broad substrate promiscuity by hydrolyzing ester bonds linked to aliphatic groups. The three-dimensional structure of the enzyme was solved in the presence and absence of substrate (tributyrin), revealing its classification within the α/β-hydrolase superfamily. Despite being a monomeric enzyme, enzymatic assays reveal a cooperative behavior with a sigmoidal profile (initial velocities vs substrate concentrations). Our investigation brings to light the allokairy/hysteresis behavior of Ade1, as evidenced by a transient burst profile during the hydrolysis of substrates such as p-nitrophenyl butyrate and p-nitrophenyl octanoate. Crystal structures of Ade1, coupled with molecular dynamics simulations, unveil the existence of multiple conformational structures within a single molecular state (E̅1). Notably, substrate binding induces a loop closure that traps the substrate in the catalytic site. Upon product release, the cap domain opens simultaneously with structural changes, transitioning the enzyme to a new molecular state (E̅2). This study advances our understanding of hysteresis/allokairy mechanisms, a temporal regulation that appears more pervasive than previously acknowledged and extends its presence to metabolic enzymes. These findings also hold potential implications for addressing human diseases associated with metabolic dysregulation.