Binding Capability Research Articles

Rapid and Specific Detection of Bacillus cereus Using Phage Protein-Based Lateral Flow Assays.

Rapid and precise diagnostic techniques are essential for identifying foodborne pathogens, including Bacillus cereus (B. cereus), which poses significant challenges to food safety. Traditional detection methods are limited by long incubation times and high costs. In this context, gold nanoparticle (AuNP)-based lateral flow assays (LFAs) are emerging as valuable tools for rapid screening. However, the use of antibodies in LFAs faces challenges, including complex production processes, ethical concerns, or variability. Here, we address these challenges by proposing an innovative approach using bacteriophage-derived proteins for pathogen detection on LFAs. We used the engineered endolysin cell-wall-binding domain (CBD) and distal tail proteins (Dit) from bacteriophages that specifically target B. cereus. The protein-binding properties, essential for the formation of efficient capture and detection biointerfaces in LFAs, were extensively characterized from the microstructural to the LFA device level. Machine-learning models leverage knowledge of the protein sequence to predict advantageous protein orientations on the nitrocellulose membrane and AuNPs. The study of the biointerface binding quantified the degree of attachment of AuNPs to bacteria, providing, for the first time, a microscopic model of the number of AuNPs binding to bacteria. It highlighted the binding of up to one hundred 40 nm AuNPs per bacterium in conditions mimicking LFAs. Eventually, phage proteins were demonstrated as efficient bioreceptors in a straightforward LFA prototype combining the two proteins, providing a rapid colorimetric response within 15 min upon the detection of 105 B. cereus cells. Recombinantly produced phage binding proteins present an opportunity to generate a customizable library of proteins with precise binding capabilities, offering a cost-effective and ethical alternative to antibodies. This study enhances our understanding of phage protein biointerfaces, laying the groundwork for their utilization as efficient bioreceptors in LFAs and rapid point-of-care diagnostic assays, thus potentially strengthening public health measures.

P110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.

As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

Charge Transfer Interaction Dynamics between 2-Methyl-8-hydroxyquinoline and 2,4-Dinitrophenol: Synthesis, Spectroscopic Characterization, DNA Binding and DFT Studies

A novel charge transfer (CT) complex was formed by combining the electron-acceptor 2,4-dinitrophenol (DNP) with the electron-donor 2-methyl-8-hydroxyquinoline (MHQ). The complex obtained was further characterized using both experimental and theoretical methods. The Benesi-Hildebrand equation can be utilized to determine various spectroscopic physical measurements such as the molar absorptivity (εCT) and formation constant (KCT). The CT complex has a stoichiometry of 1:1. Multiple spectroscopic methods were employed to investigate the resultant solid compound. The existence of charge and proton transfer in the resultant complex was confirmed by FT-IR, 1H NMR, SEM-EDX and powder-XRD studies. An electron absorption spectroscopy examination was done to analyze the complex DNA binding capability. The resulting complex was determined to have an intercalative binding mechanism, with an intrinsic binding constant (Kb) value of 4.2 × 106 M-1. The experimental results were corroborated by performing theoretical calculations using DFT using a CAM-B3LYP/6-31G(d,p) basis set. The geometrical parameters, electrostatic potential maps (MEPs) and Mullikan charges were computed and examined in agreement with the experimental observations. In addition to electron transmission, the stability of the complex is influenced by the presence of a hydrogen bond.

Leveraging Phenazine‐Based Ligands for Optimized Perovskite Optoelectronic Performance Through Chelation and Redox Engineering

AbstractPerovskite nanocrystals (PNCs) hold immense potential for optoelectronic and photovoltaic applications. However, their performance is hindered by surface defects that promote non‐radiative recombination and reduce stability. Surface engineering, particularly through defect passivation, is crucial for achieving high‐performing perovskite solar cells. Chelation has been shown to significantly improve the efficiency and stability of perovskite solar cells. In this study, a novel chelation strategy using 1,10‐Phenanthroline (Phen) is presented as a bidentate chelating ligand to effectively target and passivate these detrimental surface defects. By strategically designing a Phenanthroline derivative, dipyrido[3,2‐a:2′,3′‐c]phenazin‐11‐amine (Phen‐derivative) with optimized redox potentials, dual functionality: efficient defect passivation and hole transport is achieved. X‐ray photoelectron spectroscopy (XPS) confirms the superior binding capability of the Phen‐derivative due to chelation. This strong interaction facilitates efficient and ultrafast charge transfer from PNCs and the formation of a long‐lived charge‐separated state, as evidenced by sustained bleaching in transient absorption spectra. A metal‐dipyrido[3,2‐a:2′,3′‐c]phenazin‐11‐amine complex (Ir‐complex) derived from dipyrido[3,2‐a:2′,3′‐c]phenazin‐11‐amine, but lacking a chelation site, hinders desired hole transfer despite similar charge transfer energetics. This work emphasizes the critical role of chelation‐mediated interfacial interactions and energy alignment in designing effective charge shuttle molecules and unlocking the potential of lead‐chelating hole transporters for next‐generation light‐harvesting technologies.

Novel anti-tumor effect of natural products from Aloe vera resin and their in-vitro/in-silico targeting mechanism of carbonic anhydrase-II and IX.

Human carbonic anhydrase (hCA) plays a vital role in the development and progression of tumors in hypoxic conditions. Herein we report the hCA-II and hCA-IX activities of natural products isolated from Aloe vera (L.) Burm.f., to know their potential in tumors. These isolated compounds (1-10) displayed varying degrees of inhibition against hCA-II and hCA-IX. All the compounds showed potent activity against hCA-IX with IC50 values in the range of 2.9 - 29.1 µM. While for hCA-II, compounds 1, 2, 5-10 exhibited IC50 in the range of 4.7 - 23.4 µM. The most effective hCA IX and II inhibitors, 2 and 5, were chosen for in vitro mechanism studies, revealing that they are competitive inhibitors. Furthermore, when tested for their cytotoxic effect on BJ (normal) cell line, all the compounds showed no cytotoxic behavior, while on Prostate cancer cells (PC-3), compounds 1, 3, 5, 7, and 9 exhibited significant antiproliferative activity. Molecular docking was also conducted within the hCA IX and hCA-II active sites to observe their binding capability. Compounds 1, 5, 7, and 9 were active against both isozymes of hCA and in the PC-3 cell line, therefore these are the best choices for further in vivo studies..

Cooperative Anion-π and C-H-Cl Interactions in Multifunctional Naphthalene-Based Receptors for Chloride Recognition: Cage-Size Modulation Through Substitution Patterns.

This study introduces a novel approach for chloride recognition utilizing multifunctional naphthalene-based receptors. By strategically modifying the substitution patterns on tetrafluoropyridines, a series of new receptors with customized cavities and enhanced binding capabilities were developed. Density functional theory (DFT) calculations and experimental studies combining NMR spectroscopy and mass spectrometry confirmed the efficacy of these receptors in capturing chloride ions. The relative chloride affinity order determined experimentally is in agreement with DFT predictions. The synergistic effect of anion-π and C-H…Cl interactions, mediated by the TFP groups, played a crucial role in achieving high binding affinity. This work provides valuable insights for designing future anion receptors with improved performance.

Unveiling the therapeutic potential of azopyridine derivatives for trypsin inhibition: a DFT and In-Vitro approach

Heterocyclic azo derivatives have emerged as promising scaffolds for drug development. This study focused on the synthesis, computational analysis, and biological evaluation of a series of azopyridine derivatives (1a, 1d, 1 g, 1 h, 1 m, 1p, and 1s) as potential trypsin inhibitors. Density Functional Theory calculations indicated that derivative 1 h exhibited the lowest HOMO-LUMO energy gap 3.167 eV and was characterised as a soft molecule, suggesting strong binding capabilities. Molecular docking studies confirmed that 1 h binds favourably to the active site of trypsin with a glide score of −6.581 kcal/mol and binding energy of −29.95 kcal/mol. Along with docking studies, the stability of the trypsin-1 h complex was further analyzed using molecular dynamic simulations at 200 ns. The results showed that the ligand molecule 1 h bound strongly at the active site of trypsin. In-vitro enzyme assays determined the IC50 value of the molecule as 100 µM, demonstrating enhanced potency. These results indicate that AzPy derivatives, particularly 1 h, hold considerable promise as therapeutic agents for inflammatory disorders and cancer, paving the way for further exploration in drug development and targeted therapies. Further research is warranted to explore 1h’s efficacy, safety, and structure-activity relationships. Highlights: DFT studies were used to classify molecules based on their softness and hardness. Molecular docking, simulation, and in-vitro studies have identified potential anti-trypsin activity of candidate molecules. Experimental and computational calculations were in close agreement.

Paracyclophane-based ionizable lipids for efficient mRNA delivery in vivo

mRNA therapeutics utilizing lipid nanoparticle (LNP) delivery technology represent a medical innovation for the treatment of various diseases. Amine-derived ionizable cationic lipids have been regarded as the pivotal component of LNPs, which often utilize commercially available small amine molecules as their cores. Given that even minor changes in the structure of ionizable lipids can result in significant differences in the delivery performance, there is a growing need to redesign the lipid amine-cores to optimize mRNA therapy. Here, we rationally design and synthesize a library of 198 paracyclophane-based ionizable lipids (PILs), which are then formulated into LNPs for mRNA delivery in vitro and in vivo. The resulting PIL LNPs displayed favorable characteristics, including appropriate particle sizes, zeta potentials, mRNA binding capability, efficacious endosomal escape, and robust mRNA delivery in vitro. Tailoring the PIL structures further enables mRNA expression specifically in the liver or simultaneously across multi-organs in vivo. Notably, the optimized PIL LNPs demonstrate superior efficacy compared to the U.S. Food and Drug Administration (FDA) approved DLin-MC3-DMA LNPs following intravenous administration. Additionally, when administered intramuscularly, our PIL LNPs exhibit higher efficacy than the SM-102 and ALC-0315 LNPs that are employed in the coronavirus disease 2019 (COVID-19) mRNA vaccines. These findings demonstrate the potential of paracyclophane-based ionizable lipids in advancing mRNA therapeutics, particularly for liver-targeted drugs and vaccines.

Tailoring the Heterointerfaces of Earth-Abundant Transition-Metal Nanoclusters on Nickel Oxide Nanosheets for Enhanced Overall Water Splitting through Electronic Structure Optimization.

Evolving highly competent and economical electrocatalysts for alkaline water electrolysis is crucial in renewable hydrogen energy technologies. The slow hydrogen evolution reaction (HER)/oxygen evolution reaction (OER) kinetics under alkaline electrolytes, still, has troubled developments in high-performance green hydrogen production systems. Herein, we demonstrate the tailoring of the interface of earth-abundant transition-metal nanoclusters (MNCs), including iron (Fe), cobalt (Co), nickel (Ni), and copper (Cu) nanoclusters on nickel oxide nanosheets (M NCs|NiO NS) through metal-support interaction for enriched overall water splitting under an alkaline electrolyte. The strong metal-metal oxide interaction allows alteration of the binding capabilities of hydrogen ions (*H) and hydroxyl ions (*OH) on Ni electrodes. Specifically, the robust interaction between Fe and NiO reveals optimized binding of H* and OH* energies, facilitating the water-splitting reaction under an alkaline electrolyte. In addition, the improved HER/OER catalytic activity is attained with the Fe NCs|NiO NS with small overpotentials of ∼62.0 and ∼380.0 mV for the HER and OER, respectively, a high mass activity of ∼90.0 A g-1, a turnover frequency of ∼5.94 s-1, and long-lasting stability via offering abundant electrochemical active sites, three-dimensional (3D) morphologies, and high dispersion of nanoclusters that provide effective charge and mass transport processes. This study provides a promising strategy for the effective design of efficient bifunctional electrocatalysts based on earth-abundant materials for alkaline water electrolyzers.

ChiA: a major player in the virulence of Crohn’s disease-associated adherent and invasive Escherichia coli (AIEC)

ABSTRACT We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn’s disease (CD)-associated adherent-invasive Escherichia coli (AIEC) and intestinal mucosa. We observed a higher abundance of chiA among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆chiA colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer’s patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.

LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules.

Caspase-11 is an innate immune pattern recognition receptor (PRR) that detects cytosolic bacterial lipopolysaccharides (LPS) through its caspase activation and recruitment domain (CARD), triggering inflammatory cell death known as pyroptosis. Caspase-11 also detects eukaryotic ( i.e. self) lipids. This observation raises the question of whether common or distinct mechanisms govern the interactions with self and nonself lipids. In this study, using biochemical, computational, and cell-based assays, we report that the caspase-11 CARD functions as a bipartite lipid-binding module. Distinct regions within the CARD bind to phosphate groups and long acyl chains of self and nonself lipids. Self-lipid binding capability is conserved across numerous caspase-11 homologs and orthologs. The symmetry in self and nonself lipid detection mechanisms enabled us to engineer an LPS-binding domain de novo , using an ancestral CARD-like domain present in the fish Amphilophus citrinellus . These findings offer critical insights into the molecular basis of LPS recognition by caspase-11 and highlight the fundamental and likely inseparable relationship between self and nonself discrimination.

Coaxial Nanofiber Binders Integrating Thin and Robust Sulfide Solid Electrolytes for High‐Performance All‐Solid‐State Lithium Battery

AbstractTo access the theoretically high energy density of sulfide‐based all‐solid‐state lithium batteries (ASSLBs), a thin and robust sulfide electrolyte membrane is essential. Given the pivotal role of binder in preserving the structural integrity and interfacial stability of sulfide electrolytes upon cycling, it is desired to integrate binding capability, toughness, and stiffness into one binder, yet remains difficult. Herein, this challenge is addressed using a nanofiber‐reinforced strategy in the solvent‐free dry‐film process. A coaxial polyvinylidene poly(vinylidene fluoride‐co‐hexafluoropropylene) @ thermoplastic polyurethane (PVDF‐HFP@TPU) nanofiber binder is embedding into a Li6PS5Cl (LPSCl) matrix to obtain a sulfide thin‐layer (LPSCl‐P@T). During hot calendering of the sulfide‐binder mixture, the PVDF‐HFP shell layer melts and tightly binds LPSCl particles. The underlying TPU core layer, which maintains the fibrous structure, reinforces the structural stability of the membrane. Particularly, the fiber‐matrix connection is improved with the assistance of the molten PVDF‐HFP, collectively contributing to the effective dissipation of the mechanical stress. Controlled fusion of the core‐shell nanofiber also leads to enhanced interfacial anchoring of the cathode and electrolyte. The assembled cells with LPSCl‐P@T deliver stable cycling performances. The PVDF‐HFP@TPU nanofiber binder overcomes the long‐existing incompatible problems between binder toughness and stiffness, and shows promises in developing high‐performance sulfide‐based ASSLBs.

Adenoviral fiber-knob based vaccination elicits efficient neutralizing antibodies and T cell responses against adenovirus infection

BackgroundHuman adenoviruses (HAdVs) frequently cause common respiratory or gastrointestinal infections among children, adults, individuals with immune deficiencies, and other vulnerable populations with varying degree of symptoms, ranging from mild to server, and in some cases, even fatalities. Despite the significant clinical impact of HAdVs, there is currently no approved vaccine available.MethodsThis study explores the potential of the adenovirus type 5 fiber knob (Ad5-FK) to stimulate the production of Ad-specific neutralizing antibodies and T-cell responses in mice. Based on structure predictions, we first expressed Ad5-FK in E. coli and confirmed the assembly of FK into its trimeric form. After testing the binding capability of the trimeric FK to susceptible cells, the immunogenicity of the protein in combination with the c-di-AMP adjuvant was assessed in BALB/c mice.ResultsThe purified Ad5-FK exhibited self-trimerization and maintained correct conformation akin to the authentic FK structure. This facilitated effective binding to susceptible HEK293 cells. Notably, the protein demonstrated significant inhibition of HEK293 cells infection by rAd5-GFP. Immunization of BALB/c mice with Ad5-FK, or Ad5-FK mixed with c-di-AMP yielded FK-specific antibodies with potent neutralization capacity. Significantly, Ad5-FK was found to elicit a vigorous CD4+ T-cell response in the immunized mice.ConclusionOur findings underscore the efficacy of FK-based vaccine in eliciting anti-Ad humoral immune response and CD4 T-cell immune reactions essential for protection against viral infections.

Computer-Aided Site-Specific PEGylation of PET Hydrolases for Enhanced PET Degradation.

The enormous accumulation of poly(ethylene terephthalate) (PET) waste has posed a serious threat to the environment and human health, and biodegradation with PET hydrolase (PETase) can be a possible solution. Herein, we propose site-specifically modifying PETase with amphiphilic polymers to improve the enzyme performance at ambient temperature. For this purpose, we devise a computer-aided strategy to prioritize the conjugation site, and polyethylene glycol (PEG) preparations of 0.55 to 10 kDa are site-specifically conjugated to PETase. The most active conjugate PETase-PEG 5k (PETase-5K) shows an increase of melting temperature (3.88 °C) and significantly improves PET degradation performance (3.5- and 3.1-fold increases at 30 and 40 °C, respectively). Experimental investigation and molecular dynamics simulations reveal that the site-specific PEGylation increases the hydrophobic solvent-accessible surface area and the binding capability to the PET surface, thickens the hydration layer, increases the intramolecular hydrogen bonding, reduces the interactions between water and the conjugated enzyme surface, and rigidifies the enzyme structure via hydrogen bonding and hydrophobic interactions between the polymer and the enzyme, thus leading to improved enzymatic performance of PETase-5K. We further validate the versatility of the site-specific PEGylation in one of the most evolved variants of PETase, FAST-PETase, by 1.8-fold improvement in PET degradation at 30 °C. The presented computer-aided site-specific conjugation strategy has opened a new avenue to enhancing PETase performance at ambient temperature, and the contribution of PEGylation to PETase unraveled in this work laid a foundation for the rational engineering of PET hydrolases.

Development of deep learning software to improve HPLC and GC predictions using a new crown-ether based mesogenic stationary phase and beyond

The application of AI to analytical and separative sciences is a recent challenge that offers new perspectives in terms of data prediction. In this work, we report an AI-based software, named Chrompredict 1.0, which based on chromatographic data of a novel mesogenic crown ether stationary phase (CESP). Its molecular design represents a significant advancement due to the unique combination of properties and binding capabilities, including the formation of a cavity, mesogenic behavior via mobile chains, and a range of polar and non-polar interactions (aromatic rings, N=N and O=O double bonds, alkyl chains, π–π interactions, and hydrogen bonding). The mesogenic phase is effective in both normal and reversed-phase chromatography, enhancing the software's adaptability across diverse datasets.Here we introduce for the first time an unprecedented scientific approach, integrating deep learning techniques with the novel CESP, which demonstrates exceptional thermal and analytical performance in both liquid chromatography modes, especially in the separation of complex hydrocarbon isomers. This ability enables the results obtained with CESP to extend across various types of stationary phases.Leveraging these insights, a comprehensive chromatographic dataset on a series of aromatic and polyaromatic molecules interacting with our CESP was used to train a Deep Learning Model (DLM). This model is embedded within a user-friendly software, Chrompredict 1.0, designed for predicting chromatographic parameters (MAE = 0.042, R² = 0.95) by selecting chemical descriptors directly from SMILES notation. It offers a deeper understanding of molecular structure and interactions through exploratory data analysis, identifying key factors affecting model accuracy and chromatographic behavior.Users can configure hyperparameters, choose from six machine learning models, and compare their performance with DLM. Chrompredict 1.0 excels in retention behavior prediction for compounds with known structures, and it accurately predicts chromatographic retention and thermal characteristics for different temperatures in HPLC and GC. The model has been successfully tested with METLIN database of 1,023 small molecules of diverse structures and polarities (R² > 0.75, error range ±7.8 s). Overall, the CESP, combined with Chrompredict 1.0, offers a robust tool for intelligent chromatographic analysis, encompassing chemo-informatics, statistical analysis, and graphical capabilities across a broad range of compounds and stationary phases.

Hemoglobin targeting potential of aminocarb pesticide: Investigation into dynamics, conformational stability, and energetics in solvent environment

Aminocarb (AMC), a carbamate pesticide, due to its prevalent usage exhibits increased accumulation in the environment affecting both insects and humans. It enters the human body via food grains and be transported through bloodstream. AMC's chemical structure, containing specific molecular frameworks and functional groups, enables it to bind with proteins like albumin and hemoglobin. Given that molecules with similar architecture are known to bind with hemoglobin, we aimed to explore Aminocarb's binding capability and the potential mechanism or mode of its interaction with hemoglobin. Hb being a tetramer with a profound interface between amino acid chains offers multiple binding sites. It is therefore important to investigate the structural aspects of binding of AMC by employing various spectroscopic and in-silico methods. The surface of the α1 chain near the α1β2 interface emerges as the preferred binding site for AMC, primarily due to its conformational restrictions. In its bound state, AMC tends to maintain a relaxed conformation, closely resembling its globally optimized geometry, and resides in close proximity to the α1 chain via multiple hydrophobic contacts and water bridge as observed in molecular dynamics (MD) simulations. Fluorescence quenching experiments showed moderate binding strength (7.7 × 10⁴ L M⁻1 at 288 K, 7.8 × 10⁴ L M⁻1 at 298 K, 7.9 × 10⁴ L M⁻1 at 308 K) and spontaneous binding, driven by hydrophobic and van der Waals interactions, as indicated by enthalpy (0.80–0.91 kJ mol⁻1), entropy (0.0970–0.0974 kJ mol⁻1), and Gibbs free energy (−27.13 to - 29.08 kJ mol⁻1). Circular dichroism experiments reveal no major structural changes in Hb. Quantum chemical calculations and MD simulations reveal conformation-dependent energy differences, enhancing our understanding of AMC's binding mechanism to Hb.

Design of Novel Naphthalimidopropanediol Derivatives as Staphylococcus Aureus Antibacterial Agents Utilizing 3D‐QSAR, ADMET, Molecular Docking, and Dynamics Simulations

AbstractStaphylococcus aureus is a prevalent foodborne pathogen, and its resistance has become more pronounced due to antibiotic overuse. In this paper, we constructed a 3D‐QSAR model using 47 naphthalimidopropanediols derivatives (NIOLs). The results indicate that the CoMFA model (q2 = 0.771, r2 = 0.998) and CoMSIA‐ASH model (q2 = 0.638, r2 = 0.995) exhibit favorable predictive capabilities, leading to the design of 11 novel NIOLs as antibacterial agents. ADMET was used to validate their pharmacokinetic characteristics, molecular docking was performed to validate the binding capability of the designed molecules, dynamics simulations, and binding free energy were employed to verify the accuracy of docking results. The results demonstrate excellent performance of the designed novel molecules, which may provide significant references for the development of novel and effective antibacterial agents against S. aureus.

Interaction between pea protein isolate and quercetin: Effects on protein conformation and quercetin activity.

Comprehensive comprehension of the interaction between proteins and polyphenols is crucial for advancing their utilization in food processing. This study investigated no-covalent interaction between pea protein isolate (PPI) and quercetin (Que) through spectroscopic analysis and molecular simulation. Fourier transform infrared spectroscopy and circular dichroism spectrum showed that the interaction between PPI and Que changed the secondary structure of the protein due to a decrease in α-helix content and an increase in the random coil. Thermodynamic parameters indicated that the Quebound PPI via hydrogen bonds and hydrophobic interactions (ΔH>0, ΔS>0, and ΔG<0), which was also confirmed by molecular docking. Particle size and ζ-potential showed that PPI and Que demonstrated effective interaction and binding capabilities, enhancing the stability. In addition, the antioxidant and bioaccessibility of complexes have also been enhanced. This study shed a light on the application of protein-polyphenol complexes for developing functional foods. PRACTICAL APPLICATION: Interaction between pea protein isolate and quercetin can change the protein conformation to maintain the stability of quercetin and is helpful to expand the market value and application value of plant protein. The research has important implications for using leguminous protein as embedded support to improve the stability of polyphenols compounds.

High temperature mechanical properties and tribological behavior of nacre-inspired Ti (C, N)/Al-Cu composites

In order to improve the toughness of aluminum matrix composites with high ceramic contents, nacre-inspired Ti (C, N)/Al-Cu composites are prepared via freeze casting and pressure infiltration, and their mechanical properties and tribological behavior are investigated. The prepared composites can maintain excellent compressive strength, hardness and wear resistance when the experimental temperature increases from 25 °C to 300 °C. This can be attributed to the stable load bearing capacity of the Ti (C, N) ceramic layer at high temperature, the high interface binding capability between Ti (C, N) and Al, as well as the high crack growth inhibition ability of “layered network” structures. Moreover, the tribo-oxide layer formed during the wear process can further improve the wear resistance of the composites.

PQSAR-guided Genetic Evolution of Peptide Ligands toward Improved Binding Capability to Rheumatic Immune-related Prk Polo-box Domain

Human Prk kinase plays an important role in the maintenance of inflammatory stability and has been established as an attractive target of diverse rheumatic immune diseases. The kinase possesses a highly conserved polo-box domain (PBD) in its C-terminal noncatalytic region, which exhibits a wide specificity across its various substrates to regulate the kinase-mediated substrate phosphorylation. In this study, peptide quantitative structure-activity relationship (pQSAR) was systematically modeled based on a gene ontology-enriched set of Prk PBD-binding peptide data, which was structurally characterized using global descriptors and statistically correlated with peptide affinities via both linear and nonlinear machine learning regressions. The optimal pQSAR predictor was then employed to guide the genetic evolution (GE) of a random peptide group toward improved potency to Prk PBD domain, from which a number of hits were measured to have moderate or high affinity. The resulting Pm7 peptide was determined as a good binder that can effectively interact with the domain at sub-micromolar level, which was then used as a parent template to further derive other promising candidates by combining systematic residue mutagenesis and structure-based rescoring. Two Pm7-derived counterparts Pm72 and Pm74 were rationally designed to exhibit a satisfactory binding profile to Prk PBD domain, with affinity improved by 3.1-fold and 4.6-fold relative to their parent Pm7. Structural and energetic analyses revealed that the potent Prk PBD-binding sequences can be divided into a N-terminal polar section, a middle positively charged anchor and a C-terminal hydrophobic section, thus conferring both stability and specificity to the domain-peptide recognition and association.