Search Results (601)

Background: The ability of synthetic plastics to persist in the environment and the accumulation of microplastics has intensified the need to explore biological mechanisms capable of interacting with, and possibly degrading, polymeric materials. Microbial enzymes that have extensive catalytic flexibility represent promising candidates in this context. Aim: This study set out to examine the molecular interaction patterns and dynamical stability of Pseudomonas aeruginosa elastase (LasB) with representative structural fragments of typical synthetic plastics to assess the suitability of the enzyme to polymer-derived substrates. Methods: The crystallographic structure of LasB (PDB ID: 1EZM) was retrieved from the Protein Data Bank and pre-prepared with the help of AutoDock4.2.6 Tools. Those polymer-derived ligands that were associated with the major industrial plastics such as polyamide (PA), polyvinyl chloride (PVC), polycarbonate (PC), poly-ethylene terephthalate (PET), polymethyl methacrylate (PMMA), and polyurethane (PUR) were retrieved in the PubChem database and geometrically optimized with the help of the MMFF94 force field. AutoDock Vina, with a specific grid box around the catalytic pocket, including Zn²⁺ ion, was used to perform molecular docking simulations. PyMOL and BIOVIA Discovery Studio software were used to analyze binding conformations, interaction residues and types of intermolecular contacts. Phosphoramidon, a known metalloprotease inhibitor, served as a positive control to confirm the docking protocol. Additional assessment of the structural stability and conformational behavior of the enzyme–ligand complexes was conducted by molecular dynamics (MD) simulations with the Desmond engine and explicit solvent model in a 50 ns trajectory using the OPLS4 force field. RMSD, RMSF, radius of gyration, hydrogen bonding analysis and solvent accessibility parameters were used to measure structural stability. Results: The docking experiment showed varying binding affinities with the test polymers. Polycarbonate (−5.774 kcal/mol) and polyurethane (−5.707 kcal/mol) had the highest in-teractions with the LasB catalytic pocket, polyamide (−5.277 kcal/mol) and PET (−4.483 kcal/mol) followed PMMA and PVC, which had weaker affinities. The following were the important residues involved in interaction networks: Glu141, His140, Val137, Arg198, Tyr114, and Trp115 that were implicated in interaction networks with hydrophobic interactions, π-cation interactions and van der Waals forces that were the major stabilization forces. MD simulations had stabilized complexes, and RMSD values were found to be within acceptable ranges of stability, and ligand-specific changes (around 1.0-3.2 A), which is also in line with stable protein-ligand systems. Phosphoramidon used as a positive control had an RMSD of 1.205 A which is within this stability range. PCA determined various ligand-bound conformational states of LasB with PA in com-pact state, PC and PVC in intermediate states and PUR, PMMA and PET in ex-panded conformations, indicating structur-al stability and adaptability of the binding pocket. Conclusion: These findings show that LasB has a structurally flexible catalytic pocket that can accommodate a wide range of polymer-derived ligands. These results offer an insight into the recognition of enzymes with polymers at the molecular level and also indicate that LasB might help in the interaction of microorganisms with synthetic plastics in environmental systems. Full article

In the pathological cascade of cerebral ischemia, the pyroptosis axis mediated by the NLRP3 inflammasome in activated microglia is a core link driving neuroinflammation and secondary brain injury. Quercetin has been proven to possess multi-target neuroprotective activity, and its anti-inflammatory effect has attracted particular attention. However, direct molecular evidence is lacking regarding how quercetin precisely regulates the NLRP3/Caspase-1/GSDMD core pyroptosis axis in microglia in cerebral ischemia models and whether it can directly target NLRP3 to inhibit this axis, thereby alleviating cerebral ischemic injury. This study aimed to investigate the molecular mechanism by which quercetin alleviates cerebral ischemic injury through inhibiting the pyroptosis axis, combining cellular and animal models with molecular docking and molecular dynamics simulations. The oxygen-glucose deprivation (OGD) model of BV2 microglia and the photothrombotic (PT) model of focal cortical ischemia in male C57BL/6 mice were used to detect the ameliorative effect of quercetin on cerebral ischemia-related injury through cellular and animal experiments. AutoDock Vina 1.5.7 and GROMACS 2025.3 software were employed for molecular docking and molecular dynamics simulations, respectively, to analyze the binding mode and complex stability between quercetin and the NLRP3 protein. The results showed that quercetin could significantly ameliorate OGD-induced injury in BV2 cells and downregulate the expression of pyroptosis and inflammation-related proteins and factors. Meanwhile, it relieved motor dysfunction in PT mice, attenuated cortical neuronal injury, and inhibited the activation of the cerebral pyroptosis axis. At the molecular level, molecular simulation predictions indicated that quercetin might specifically bind to the NACHT domain of the NLRP3 protein, forming a complex with a stable conformation, and van der Waals interactions served as the main driving force for binding. This study confirmed that quercetin can directly bind to the NLRP3 protein and alleviate cerebral ischemia-induced inflammatory injury by inhibiting the activation of the NLRP3/Caspase-1/GSDMD pyroptosis axis and the release of downstream inflammatory factors. Combined with the molecular simulation results, a predictive hypothesis is proposed: direct binding of quercetin to the NLRP3 protein is one of its core mechanisms of action. These findings provide direct experimental evidence for the development of NLRP3-based drugs against ischemic brain injury. Full article

The dangerous potential of chemical warfare requires immediate development of new materials capable of detecting and efficiently adsorbing the toxic nerve agents VX and Novichok (A-234). The current adsorbents fail to achieve sufficient detection efficiency and specific binding capabilities. Our research, conducted through advanced computational modeling, predicts that carbon nanocones (CNCs) could function as effective molecular traps for these toxic substances. The research combines density functional theory (DFT) with molecular dynamics (MD) and Monte Carlo (MC) simulations to explain the basic principles of molecular trapping by these agents. The nanocone shape produces two distinct and selective binding areas. MC shows preferential trapping VX molecules within the internal concave surface (P1), while A-234 molecules are strongly adsorbed on the external convex surface (P2). Docking results complement this by showing that A-234 exhibits stronger single-molecule binding on the more open surface, consistent with its preference for P2. The nanocone captures molecules through van der Waals forces, which produce measurable electronic changes that modify its electronic signature. The research demonstrates that carbon nanocones represent a promising candidate material for the future development of chemical defense systems, potentially including sensitive detection systems and advanced filtration technologies. Full article

Persimmon polyphenols (PP) are natural polyphenols with high reactivity and strong deodorization potential; however, their practical application in odor control is limited by their poor solubility. In this study, natural deep eutectic solvents (NADESs) were employed for the green extraction of PP, and the capabilities of extracts on the removal of ammonia (NH₃) and hydrogen sulfide (H₂S) were investigated. In addition, the underlying mechanisms were explored by integrating spectroscopic analysis, molecular dynamics simulations, and quantum chemical calculations. The results showed that chloride-citric acid (CC-CA) was the optimal system in both PP extraction and sustained NH₃ removal, while the betaine-urea (B-U) system was more effective for H₂S removal. NH₃ removal was governed by acid-base neutralization, with the resulting ammonium species being further stabilized within the PP-regulated NADES hydrogen-bond network. In contrast, H₂S interacted with the solvent network not only through acid-base neutralization but also via Van der Waals forces and hydrophobic contacts. Our data supported that NADESs enhanced the deodorization performance of PP through cooperative microenvironment regulation rather than irreversible chemical conversion. This work highlighted that NADESs could not only function as highly efficient extraction media for polyphenols, but also active platforms for enhancing selective gas-capture capability for polyphenols. Furthermore, it provided a new strategy for the rational design of green, persimmon-derived deodorants. Full article

While graphene-based lubricants are well-studied, the tribological potential of emerging carbon–nitride and carbon–boron 2D materials remains largely unexplored. Herein, by using first-principles calculations implemented in the VASP code, we systematically explored the interlayer interactions and frictional properties of bilayer homojunctions and heterostructures composed of graphene, C₃N, and C₃B. The DFT-D3 dispersion correction was employed to accurately capture the interlayer van der Waals forces. The results reveal that C₃N/C₃N, C₃N/graphene (C₃N/Gra), and C₃B/graphene (C₃B/Gra) systems exhibit significantly lower friction coefficients compared to pristine bilayer graphene (Gra/Gra). Notably, the sliding potential barrier of the C₃N/Gra heterostructure is only ~0.45 meV/atom (approximately 1/10 that of the Gra/Gra system), manifesting exceptional superlubricity and considerable potential for superlubricant applications. The sliding potential barrier of the C₃B/C₃N heterostructure is slightly smaller than that of Gra/Gra. In contrast, the C₃B/C₃B homojunction exhibits high resistance to sliding; under normal loads of 1–4 nN, its potential barrier ranges from ~16 to ~115 meV/atom, which is consistently twice that of Gra/Gra. The observed frictional variations are attributed to sliding-induced interfacial charge redistribution. These findings provide fundamental insights into the tribological behavior of C₃N- and C₃B-based materials and establish a quantitative link between frictional properties and interfacial charge dynamics, offering a theoretical basis for the development of advanced graphene-derived lubricants. Full article

CD38 is a multifunctional enzyme that plays a pivotal role in NAD⁺ metabolism and calcium signaling, and its abnormal activity is closely associated with multiple myeloma, age-related metabolic decline, neurodegenerative diseases, and other disorders. Although monoclonal antibodies such as daratumumab have been approved for clinical application, their inherent limitations necessitate the development of novel small-molecule CD38 inhibitors. In this study, we employed DNA-encoded library (DEL) technology for the high-throughput screening of CD38 inhibitors, using a DEL library containing more than 100,000 unique compounds to screen against recombinant human CD38. A total of 1043 enriched compounds were initially identified, and after rigorous validation and screening to exclude non-specific binding and previously reported active compounds, eight hit compounds with diverse chemical scaffolds were obtained, among which Fenbendazole—a clinically approved antiparasitic drug—was included. Surface plasmon resonance (SPR) assays confirmed the direct binding of these hit compounds to CD38, with dissociation constants (KD) ranging from 7.74 × 10⁻⁵ M to 2.15 × 10⁻⁴ M. Fluorescence-based enzymatic activity assays demonstrated that these compounds exert dose-dependent inhibitory effects on both the hydrolase (with ε-NAD as substrate) and cyclase (with NGD as substrate) activities of CD38. Further structure–activity relationship (SAR) analysis of Fenbendazole analogues revealed the critical structural features that regulate CD38 inhibitory potency, and Flubendazole was found to exhibit excellent inhibitory activity, with an IC₅₀ of 14.78 ± 4.21 μM against CD38 hydrolase and 26.31 ± 3.40 μM against cyclase. Molecular docking and 100 ns molecular dynamics (MD) simulations further elucidated the molecular mechanism of CD38 inhibition by lead compounds, confirming that van der Waals interactions are the main driving force for the binding of small-molecule ligands to CD38, with conserved aromatic residues in the active site mediating ligand recognition. This study validates DEL technology as an efficient and reliable platform for the discovery of CD38 inhibitors, and the identified lead compounds—especially Fenbendazole and its analog Flubendazole—provide valuable molecular scaffolds for the further structural optimization of CD38 inhibitors. These findings lay a solid foundation for the development of novel therapeutic agents for the treatment of CD38-associated diseases. Full article

With ongoing development in the process industries, the accumulation of industrial inorganic solid wastes (IISWs) has become increasingly significant. IISWs are characterized by large volume and toxicity and pose challenges in treatment and control. IISWs from chemical processes mainly include red mud (RM), zinc slag, lithium slag (LS), electrolytic manganese residue (EMR), phosphogypsum (PG), water treatment sludge (WTS), sewage sludge, blast furnace slag (BFS), steel slag (SS), coal fly ash (CFA), coal gasification slag (CGS), copper smelting slag (CSS), and lead smelting slag (LSS). Having been chemically processed, they exhibit complex compositions that pose challenges for further utilization. In this paper, we comprehensively review the preparation of adsorbents from IISWs as raw materials, the applications of IISW-derived adsorbents, and their adsorption mechanisms. The obtained adsorbents include modified IISWs, zeolites, porous ceramics, and composite and hybrid adsorbents. The adsorption mechanisms, such as van der Waals forces, electrostatic interactions, and π–π interactions, contribute to the rapid adsorption kinetics and high adsorption capacity observed in these adsorbents. Full article

Cyclooxygenase-2 (COX-2) is a key enzyme in inflammatory pathways and serves as a therapeutic target in the treatment of inflammation-related diseases. Curcumin, a bioactive polyphenol from turmeric, has gained scientific attention due to its potent anti-inflammatory properties, largely mediated through COX-2 inhibition. However, the poor solubility and limited bioavailability of Curcumin limit its potential as a therapeutic agent targeting inflammatory diseases. We used an in silico approach to identify Curcumin-like scaffolds as novel COX-2 inhibitors with improved drug-like properties and therapeutic potential. A pharmacophore model derived from the key binding moieties of Curcumin was used to virtually screen the ZINC-22 database, identifying 237 candidate compounds for further evaluation. Molecular docking further prioritized these compounds to 10 candidates with the highest binding affinities. Most hits obeyed Lipinski’s rules, except for ZINC32605424 and ZINC47133707, which exhibited high LogP and molecular weight, respectively. Toxicity screening indicated that ZINC47133693 and ZINC09499196 exhibited high safety profiles, with ZINC15942488 being highly toxic. Furthermore, certain hits such as ZINC32605424 and ZINC15942488 were predicted to be P-glycoprotein substrates and potential inhibitors of cytochrome P450. Molecular dynamics simulations confirmed the stability of COX-2–ligand complexes, with critical interactions observed at conserved residues Tyr323 and Leu320. Binding energy calculations identified ZINC32605424 as the strongest COX-2 binder, mainly stabilized by Van der Waals forces. Overall, compounds such as ZINC32605424, ZINC08644750, ZINC47133693, and ZINC09499196 demonstrated potent COX-2 inhibition. These candidates show strong potential for further preclinical validation in studies investigating inflammation-related metabolic complications. Full article

Hydrogen energy has garnered widespread attention as a clean energy source. This study employs density functional theory (DFT) to systematically investigate the hydrogen storage performance of Be_n(n = 10–12) clusters. The results reveal that hollow spherical Be_n clusters exhibit excellent hydrogen storage capacity while maintaining good thermal stability even after H₂ adsorption at room temperature. Specifically, Be₁₀, Be₁₁ and Be₁₂ clusters can adsorb 26, 28, and 30 H₂ molecules, achieving hydrogen storage densities of 31.96 wt%, 31.87 wt%, and 35.87 wt%, respectively—far exceeding the U.S. Department of Energy’s target of 5.5 wt%. Calculations indicate an average adsorption energy between 0.16 and 0.19 eV/H₂, which lies between physisorption and chemisorption. IGMH isosurface analysis confirms the physisorption characteristics of H₂ molecules. PDOS analysis reveals that the hydrogen storage mechanism primarily originates from H₂ molecular polarization and van der Waals forces arising from orbital hybridization between hydrogen atoms and the substrate. Desorption temperature calculations show that, above 216 K, this material demonstrates potential for reversible hydrogen storage. This study demonstrates that these three hollow spherical beryllium cluster systems are ideal candidates for achieving ultra-high-capacity reversible hydrogen storage. Full article

The pressing need for sustainable, plant-based alternatives is highlighted by the growing resistance of agricultural pests to synthetic pesticides. This study examined the pesticidal potential of phytocompounds from C. tora discovered by GC–MS analysis against important tomato insect (T. absoluta) and fungal pathogen (A. solani). The binding stability and interaction dynamics of specific metabolites with fungal virulence (polygalacturonase, MAP kinase HOG1, and effector AsCEP50) and insect neuromuscular (ryanodine receptor and sodium channel protein) targets were assessed using molecular docking and 100 ns molecular dynamics simulations. Among the screened compounds, squalene and 4,7,10,13,16,19-docosahexaenoic acid, methyl ester (DHAME) exhibited the strongest binding affinities and conformational stability, with MM-GBSA binding free energies of −38.09 kcal·mol⁻¹ and −52.81 kcal·mol⁻¹ for squalene complexes in T. absoluta and A. solani, respectively. Persistent hydrophobic and mixed hydrophobic–polar contacts that stabilised active-site residues and limited protein flexibility were found by ProLIF analysis. These lively and dynamic profiles imply that DHAME and squalene may interfere with calcium signalling and stress-response pathways, which are essential for the survival and pathogenicity of pests. Hydrophobic interactions were further confirmed as the primary stabilising force by the preponderance of van der Waals and nonpolar solvation energies. The findings show that C. tora metabolites, especially squalene and DHAME, are promising environmentally friendly biopesticide candidates that have both insecticidal and antifungal properties. Their development as sustainable substitutes in integrated pest management systems are supported by their stability, binding efficacy and predicted biosafety. Full article

Estimating the adsorption data and understanding the adsorption behavior and mechanism of organic pollutants on nanoplastics are crucial for assessing their ecological risks. Herein, in silico techniques, i.e., grand canonical Monte Carlo simulations, density functional theory computations, and quantitative structure activity relationship (QSAR) modeling, were integrated to examine the adsorption of 39 representative aliphatic and aromatic compounds and nine emerging pollutants (brominated flame retardants and phosphorus flame retardants) onto 12 different nanoplastics under atmospheric conditions. Three QSAR models were constructed to predict the adsorption equilibrium constant (logK) for polyethylene, polyoxymethylene, and polyvinyl alcohol nanoplastics individually, along with 12 QSAR models for separately estimating adsorption capacities (C_m) on different nanoplastics. Furthermore, a novel multi-dimensional prediction model was developed, enabling simultaneous, high-throughput prediction of adsorption capacities across multiple nanoplastics and pollutants with a single input. These results revealed that van der Waals and electrostatic interactions serve as the primary driving forces for the adsorption. The novel multi-dimensional prediction model facilitates rapid and comprehensive assessment of pollutant–nanoplastic interactions with one-click, and paves the way for improved risk evaluations and advancing predictive environmental research. Full article

This study provides a comprehensive overview of research and advancements on carbon materials with regard to practical targets for hydrogen storage in terms of gravimetric and volumetric capacities. For the sake of clarity, only the most relevant references on hydrogen storage by adsorption are presented, although the study was conducted in the same exhaustive manner as the one initially carried out by Anne C. Dillon and Michael J. Heben in 2001 with a particular emphasis on emerging technologies and potential applications in various sectors. This study also focuses on the importance of carbon-based materials with high specific surface areas and porous structures optimised to maximise adsorption—including at high pressure—while primarily limiting references herein to experimentally validated results. It therefore offers insights into the porous materials, as well as the methodologies—including a fully comprehensive and so-far proven highly transferable intermolecular hydrogen model combining van der Waals’s and Coulomb’s forces—used to improve hydrogen solid storage efficiency. Full article

Electric-field-sensitive dielectrics play a crucial role in electric field induction sensing and related capacitive conversion, with interfacial polarization and charge accumulation largely determining the signal output. This paper introduces graphene/transition metal dichalcogenide (TMD) (MoSe₂, MoS₂, and WS₂) heterojunctions as functional fillers to enhance the dielectric response and electric-field-induced voltage output of flexible polydimethylsiloxane (PDMS) composites. Density functional theory (DFT) calculations were used to evaluate the stability of the heterojunctions and interfacial electronic modulation, including binding behavior, charge redistribution, and Fermi level-referenced band structure/total density of states (TDOS) characteristics. The calculations show that the graphene/TMD interface is primarily controlled by van der Waals forces, exhibiting negative binding energy and significant interfacial charge rearrangement. Based on these theoretical results, graphene/TMD heterojunction powders were synthesized and incorporated into polydimethylsiloxane (PDMS). Structural characterization confirmed the presence of face-to-face interfacial contacts and consistent elemental co-localization within the heterojunction filler. Dielectric spectroscopy analysis revealed an overall improvement in the dielectric constant of the composite materials while maintaining a stable loss trend within the studied frequency range. More importantly, calibrated electric field induction tests (based on pure PDMS) showed a significant enhancement in the voltage response of all heterojunction composite materials, with the WS₂-G/PDMS system exhibiting the best performance, exhibiting an electric-field-induced voltage amplitude 7.607% higher than that of pure PDMS. This work establishes a microscopic-to-macroscopic correlation between interfacial electronic modulation and electric-field-sensitive dielectric properties, providing a feasible interface engineering strategy for high-performance flexible dielectric sensing materials. Full article

Background: Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobic, immobile oral bacterium responsible for the secretion of virulence factors, namely leukotoxin (LtxA), a large exotoxin of the RTX family that enables the bacterium to evade the immune system by destroying leukocytes, resulting in aggressive periodontitis (AP) leading to tooth loss. Methods: This study aimed to screen 106 molecules derived from Moroccan propolis in order to identify potential inhibitors of the active sites of LtxA based on molecular docking, ADMET property evaluation, and molecular dynamics (MD) simulation. Results: Epigallocatechin gallate (EGCg), used as a reference compound, showed binding energies of −6.9 kcal/mol, −6.1 kcal/mol, −6.5 kcal/mol, and −5.9 kcal/mol with the four active sites P1, P2, P3, and P4, respectively. By establishing conventional hydrogen bonds, pi-alkyl bonds, and non-covalent pi–pi bonds. Chrysin and luteolin showed favorable binding affinities with the four active sites, named as follows: P1–P4 (P1–chrysin = −7.5 kcal/mol; P2–chrysin = −7.9 kcal/mol; P3–chrysin = −8.1 kcal/mol; P4–chrysin = −6.9 kcal/mol; P1–luteolin = −7.3 kcal/mol; P2–luteolin = −7.6 kcal/mol; P3–luteolin = −8.1 kcal/mol; P4–luteolin = −7.3 kcal/mol). The binding affinity of these two propolis derivatives was stabilized by pi−sigma bonds, pi−alkyl bonds, conventional hydrogen bonds, pi-cation interactions, non-covalent pi–pi bonds, and carbon–hydrogen bonds. According to free energy calculations performed with Prime MM-GBSA, the complexes formed by chrysin demonstrated the most stable interactions due to Van der Waals and lipophilic forces. Luteolin formed significant interactions, but slightly weaker than those of chrysin. These results reveal the inhibitory potential of chrysin and luteolin with protein active sites. MD simulations corroborated the excellent stability of complexes formed by chrysin, as indicated by low RMSD values, suggesting favorable dynamic behavior. Conclusions: These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations. Full article

Per- and polyfluoroalkyl substances (PFAS) are emerging contaminants that persist in soil environments, necessitating reliable models to predict their fate and transport. This study evaluates the performance of three theoretical models in estimating the maximum adsorption capacity (Qmax) of perfluorooctanoic acid (PFOA) on kaolinite and montmorillonite clay minerals. The models assessed include a van der Waals interaction-based approach, a monolayer adsorption capacity model, and a surface site density model emphasizing reactive hydroxyl groups at mineral edges. Benzene, nitrogen, and glyphosate molecules were used as reference compounds for model validation. Results indicated that the van der Waals model significantly underestimated Qmax (0.0007 mg·g⁻¹ for kaolinite), while the monolayer capacity model produced substantial overestimations (17.51 mg·g⁻¹) compared to the experimental range (0.10–10.0 mg·g⁻¹). The surface site density model provided the most accurate predictions (3.39 mg·g⁻¹ for kaolinite), although it slightly underestimated values for montmorillonite (0.20 mg·g⁻¹) by excluding interlayer adsorption. These discrepancies demonstrate that simplified models cannot adequately capture the complex adsorption behavior of PFAS. Accurate prediction requires site-specific approaches incorporating electrostatic forces, hydrogen bonding, and steric effects. As PFAS accumulation in soil directly contributes to groundwater contamination, improving adsorption models is essential for accurate risk assessment and the development of effective remediation strategies. Full article