Search Results (261)

Neonicotinoids are synthetic nicotine-like compounds extensively used globally as insecticides for agricultural and urban purposes. Neonicotinoid-contaminated produce is a major public health concern worldwide. Limited epidemiological studies have shown an association of neonicotinoid exposure with abnormal semen analysis. This study aimed to elucidate the potential disruption of the androgen receptor (AR) by eight common neonicotinoids, including imidacloprid (IMI), acetamiprid, clothianidin, thiamethoxam, dinotefuran, thiacloprid (THI), nitenpyram, and nithiazine using docking and molecular dynamics (MD) simulation. The results showed good binding strength of all compounds (except THI) with AR, as indicated by high binding energy, high binding affinity, and number of bonding interactions. The results of MD simulation supported the conformational stability and structural dynamic behavior of the AR-IMI (receptor-neonicotinoid) complex upon binding. This was indicated by root mean square deviation showing stability of the complex; the root mean square fluctuation showing minimized residual fluctuations upon binding; the radius of gyration showing greater compactness of the protein structure; the solvent-accessible surface area showing no changes upon binding; and the Gibbs funnel energy of the landscape showing a stable conformation state with minimum energy and slight change in size and position of the sampled energy basin of the AR, with a stable equilibrium. Taken together, the structural dynamics results showed that neonicotinoids are bound stably in the same ligand-binding domain of the AR as the native ligand testosterone. This may perturb the natural binding of testosterone with the AR and potentially disrupt downstream signaling and biological pathways, leading to male reproductive dysfunction. Full article

This study utilized a dynamic cross-linking algorithm to formulate a chemical cross-linked hydrogel model of poly(N-isopropylacrylamide) (PNIPAM) with N, N’-methylenebisacrylamide (BIS). Molecular dynamics (MD) simulations were conducted to investigate the temperature sensitivity and ibuprofen release mechanism of this hydrogel under varying cross-linking degrees and water contents. The low critical solution temperature (LCST) of the hydrogel was determined based on changes in solvent-accessible surface area (SASA) and hydrogen bond count. The LCST was found to be between 300 and 310 K. As the temperature increased, both SASA and hydrogen bond counts generally exhibited a gradual decrease. However, near the LCST, polymer chain collapse temporarily exposed the hydrophilic groups of the PNIPAM, forming hydrophilic regions that increased the contact area with water. This led to a transient increase in SASA (8% higher than that before 300 K) and hydrogen bond counts (6.25% higher than that at 290 K). Concurrently, Young’s modulus of the PNIPAM hydrogel was found to decrease with increasing water content (from 3.11 GPa to 2.59 GPa, representing a 16.7% decrease when water content increased from 0% to 50% for 80% cross-linking degree) and increase with rising cross-linking density (from 2.02 GPa to 2.94 GPa, representing a 45.5% increase when the cross-linking degree increased from 0% to 80% for 20% water content). These findings indicate that enhancing cross-linking density is an effective strategy for improving the hydrogel’s mechanical properties. A PNIPAM–ibuprofen delivery model was constructed and molecular dynamics (MD) simulations were conducted, revealing temperature dependence release behavior. Below the LCST, the PNIPAM hydrogel remains in a highly swollen state (PNIPAM single-chain radius of gyration, Rg = 0.64 nm at 290 K), with ibuprofen molecules adsorbed within the PNIPAM polymer chain network. Conversely, above the LCST, PNIPAM undergoes phase separation (Rg decreases to 0.56 nm at 320 K, representing a 12.5% decrease), resulting in volume contraction (cavity volume reduced by 35%) and disruption of the hydrogen bond network. This process results in the release of ibuprofen molecules, accompanied by an increase in their diffusion coefficient from 1.3817 × 10⁻⁹ (280 K) to 4.2847 × 10⁻⁹ m²/s (320 K). Concurrently, the interaction energy with PNIPAM experiences a decline, from −126.72 kcal/mol to −108.69 kcal/mol. The findings of this study provide insights into the optimization of the structural stability of ibuprofen delivery carriers. Full article

We use an analytical algorithm to show that the similarity measure based on the radius of gyration, still suffers from unresolved pattern recognition dilemmas. We improve the results of the radius of gyration with the y axis to prove that it is independent of the height of the trapezoidal fuzzy number, which is the key factor to constructing our counterexample. We also show that a previously developed counterexample contained questionable results. Our findings demonstrate that relying on only a few similarity measures is not sufficient to fully resolve pattern recognition dilemmas. Hence, we suggest that researchers who refer to those papers that constructed iterative algorithms with several similarity measures and repeatedly applied those measures to look for a complete solution algorithm. Full article

Using molecular dynamics simulations, we explore the impact of correlated monomer activity and star topology on the structure and dynamics of active polymers. Unlike uncorrelated active Brownian particle (ABP) stars, correlated activity induces a rather steep stretching of the star polymer at intermediate activity levels. This stretching is characterized by transitions between distinct, metastable states defined by the coordinated movement of the arms, leading to novel collective dynamics. The behavior is consistent with experimental observations of active oligomers, highlighting the critical role of activity correlations for the understanding and modeling of active polymers. Full article

Large-scale computer simulations were employed to investigate the conformational response of the spike protein components S1 and S2 using a coarse-grained model. Temperature was systematically varied to assess the balance between stabilizing residue–residue interactions and thermal fluctuations. The resulting contact profiles reveal distinct segmental reorganization and self-assembly behaviors between S1 and S2. At lower, thermoresponsive temperatures, pronounced segmental globularization occurs in the N-terminal domain (NTD; M153–K202) and receptor-binding domain (RBD; E406–E471) of S1, whereas S2 exhibits alternating regions of high and low contact density. Increasing temperature reduces this segmental globularization, leaving only minor persistence at elevated temperatures. The temperature dependence of the radius of gyration (R_g) further demonstrates the contrasting thermal behaviors of S1 and S2. For S1, R_g increases continuously and monotonically with temperature, reaching a steady-state value approximately 50% higher than that at low temperature. In contrast, S2 displays a non-monotonic response: R_g initially rises to a maximum nearly sevenfold higher than its low-temperature value, then decreases with further temperature increase. Scaling analysis of the structure factor reveals that the globularity of S1 diminishes significantly upon heating, while S2 becomes modestly more compact yet retains its predominantly fibrous character. Full article

The slow swelling rate of styrene–butadiene–styrene (SBS) in asphalt prolongs the modification process and increases energy consumption. This study proposes a novel method using benzoyl peroxide (BPO) and benzoyl methane (BPA) to accelerate SBS swelling through a radical initiation–capture mechanism. BPO generates free radicals that relax the SBS network, while BPA captures excess radicals, maintaining system stability. Molecular dynamics simulations based on the COMPASS II force field were used to analyse diffusion, radius of gyration, and solubility parameters, revealing that BPO/BPA improved SBS–asphalt compatibility and increased the diffusion coefficient by 76%. Macroscopic viscosity tests confirmed that the swelling time decreased by 40% and equilibrium viscosity increased by 39% compared with the conventional process. The modified asphalt also exhibited enhanced high- and low-temperature performance and ageing resistance. This simple and efficient synergistic technique provides a promising approach for the rapid preparation of SBS-modified asphalt and offers practical potential for industrial production. Full article

Oropouche virus (OROV), an emerging orthobunyavirus of increasing public health concern in the Americas, currently lacks approved antiviral therapies. In this study, we employed a structure-based in silico approach to identify natural antiviral scaffolds capable of targeting the Gc glycoprotein, a class II fusion protein essential for host membrane fusion and viral entry. A library of 537 plant-derived compounds was screened against the Gc head domain (PDB ID: 6H3X) through molecular docking and redocking, followed by 100-nanosecond molecular dynamics simulations, MM-PBSA free energy calculations, and ADMET profiling. Curcumin and Berberine emerged as standout candidates. Curcumin demonstrated a balanced profile, with stable binding (−38.14 kcal/mol), low backbone RMSD (1.82 Å), and consistent radius of gyration (Rg ~ 18.8 Å), suggesting strong conformational stability and compactness of the protein–ligand complex. Berberine exhibited the most favorable binding energy (−13.10 kcal/mol) and retained dynamic stability (RMSD 1.86 Å; Rg ~ 19.0 Å), though accompanied by predicted cytotoxicity that may require structural refinement. Both compounds induced reduced residue-level fluctuations (RMSF < 2.5 Å) in functionally critical regions of the Gc protein, consistent with a mechanism of action that involves stabilization of the prefusion conformation and interference with the structural transitions required for viral entry. These findings identify curcumin and berberine as promising scaffolds for anti-OROV drug development and offer a rational foundation for future experimental validation targeting viral fusion mechanisms. Full article

Elucidating amyloid formation inside biomolecular condensates requires models that resolve (i) local, chemistry specific contacts controlling β registry and (ii) mesoscale phase behavior and cluster coalescence on microsecond timescales—capabilities beyond single resolution models. We present a hybrid united atom/coarse-grained (UA–CG) force field coupling a PACE UA peptide model with the MARTINI CG framework. Cross-resolution nonbonded parameters are first optimized against all-atom side chain potentials of mean force to balance the relative strength between different types of interactions and then refined through universal parameter scaling by matching radius of gyration distributions for specific systems. We applied this approach to simulate a recently reported model system comprising the LVFFAR₉ peptide that can co-assemble into amyloid fibrils via liquid–liquid phase separation. Our ten-microsecond simulations reveal rapid droplet formation populated by micelle-like nanostructures with its inner core composed of LVFF clusters. The nanostructures can further fuse but the fusion is reaction-limited due to an electrostatic coalescence barrier. β structures emerge once clusters exceed ~10 peptides, and the LVFFAR₉ fraction modulates amyloid polymorphism, reversing parallel versus antiparallel registry at lower LVFFAR₉. These detailed insights generated from long simulations highlight the promise of our hybrid UA–CG strategy in investigating the molecular mechanisms of condensate aging. Full article

Gellan gum (Gellan), a versatile polysaccharide applied in gel formation and prebiotic formulations, is often processed to tailor its molecular properties. Previous studies employed gamma irradiation and chemical hydrolysis, though without addressing systematic scaling behavior. This study investigates the structural and conformational modifications of Gellan in dilute aqueous salt solutions using a safer and eco-friendly approach: atmospheric low-dose electron beam (e-beam) degradation coupled with viscosity analysis. Native and E-beam-treated Gellan samples (0.05 g/cm³ in 0.1 M KCl) were examined by relative viscosity at varying temperatures, with intrinsic viscosity and molar mass determined via Solomon–Ciuta and Mark–Houwink relations. Molar mass degradation followed first-order kinetics, yielding rate constants and degradation lifetimes. Structural parameters, including radius of gyration and second virial coefficient, produced scaling coefficients of 0.62 and 0.15, consistent with perturbed coil conformations in a good solvent. The shape factor confirmed preservation of an ideal random coil structure despite irradiation. Conformational flexibility was further analyzed using theoretical models. Transition state theory (TST) revealed that e-beam radiation lowered molar mass and activation energy but raised activation entropy, implying reduced flexibility alongside enhanced solvent interactions. The freely rotating chain (FRC) model estimated end-to-end distance (R_θ) and characteristic ratio (C_∞), while the worm-like chain (WLC) model quantified persistence length (l_p). Results indicated decreased R_θ, increased l_p, and largely unchanged C_∞, suggesting diminished chain flexibility without significant deviation from ideal coil behavior. Overall, this work provides new insights into Gellan’s scaling laws and flexibility under aerobic low-dose E-beam irradiation, with relevance for bioactive polysaccharide applications. Full article

Background: The pathophysiology of Alzheimer’s disease (AD) is strongly linked to damage to the cholinergic systems of the central nervous system (CNS), mainly due to the formation of β-amyloid peptide plaques, which trigger intense inflammatory responses and are currently the main cause of the symptoms of the disease. Among the therapeutic strategies under investigation, classes of natural products with immunomodulatory properties, action on the CNS, and potent antioxidant activity, which contribute to neuroprotection, stand out. Methods: We aimed to evaluate the flavonoid quercetin using in silico, in vitro, and in vivo methods for the treatment of AD. Initially, the compounds were selected, and molecular dynamics simulations were performed. The in vitro assays included tests of antioxidant activity (DPPH), enzymatic inhibition of acetylcholinesterase (AChE), and prediction of oral toxicity. The in vivo studies investigated the effects on scopolamine-induced learning deficits and conducted histopathological analysis of the brain. Results: Quercetin showed structural stability in the complex with (AChE), with no significant alterations in the Root Mean Square Deviation (RMSD), SASA and radius of gyration (Rg) parameters. Through the same method it was possible to predict stability between the quercetin and inducible nitric oxide synthase (iNOS) complex, a possible mechanism for quercetin immunomodulation in the CNS. In the AChE inhibition test, the IC₅₀ obtained for quercetin was 59.15 μg mL⁻¹, while in the antioxidant test with DPPH, the concentration of 33.1 µM exhibited 50% of the scavenging of reactive oxygen species. This corroborates the perspective of quercetin having neuroprotective activity. This activity was also corroborated in vivo, in a zebrafish model, in which quercetin reduced the cognitive deficit induced by scopolamine. Histopathological analysis revealed its ability to prevent atrophy, caused by scopolamine, in the nervous tissue of animals, reinforcing the potential of quercetin as a neuroprotective agent. Conclusions: The results of the tests carried out with quercetin suggest that this molecule has antioxidant, AChE inhibitory, and neuroprotective activities, making it a good candidate for use in future clinical trials to ensure its efficacy and safety. Full article

This paper presents an optimisation study to determine the best centre of gravity (CoG) position to improve seakeeping performance. Two varied parameters used in this study were the longitudinal and vertical centre of gravity (LCG and VCG). The Radius Gyration in the y-axis ($R_y$) is introduced as a novel single-objective function to be minimised, avoiding the complexity of the conventional seakeeping optimisation process. The quality of the seakeeping performance was evaluated by response amplitude operators (RAOs) of the heave, pitch, and vertical motion. Two different hull forms are compared to investigate the applicability of the $R_y$ as the objective function in seakeeping optimisation. The patrol boat and S-60 hull form are selected as representatives of a planing hull type and a displacement hull type. The optimisation was carried out by using the Central Composite Design (CCD) and response surface methodology (RSM) to model the relationship between the CoG and $R_y$ from large and small vessels, with the objective function minimising the $R_y$. The finding shows that minimising the $R_y$ is more sensitive to the planing hull type compared to the displacement hull type in reducing the vertical motion in different Froude numbers and wave headings. Full article

The rubber industry is evolving by incorporating innovative tools to improve production processes. A proper manufacturing process determines the behavior and service life of the resulting products. In this research, molecular dynamics simulations were used to study the effect of temperature in the cured structure on the resulting mechanical properties of EPDM. The results of the simulations at different temperatures of the crosslinked ethylene–propylene–diene monomer (EPDM) were then compared in terms of the radius of gyration, free volume, root mean square displacement, stress curves, viscosity, and gel point. Then, using the superposition principle, viscosity and tensile stress were evaluated. The molecular dynamics superposition results could reasonably predict the mechanical behavior of EPDM during and after the injection process. The results provide new insights into the molecular-level crosslinking mechanisms of amorphous polymers and their influence on mechanical behavior, which facilitates the design of the injection process for rubber component applications. The results show an increase in viscosity and a decrease in the critical gel point with increasing temperature. The hardness tests performed on an automotive component demonstrate that this has an impact on the resulting properties. Full article

The complex composition of lubricating base oils makes it difficult to analyze the influence of specific molecular structure on lubricating performance. To achieve this target, nine kinds of poly α-olefin molecules with different structure characteristics were designed, which prepared the lubricant models. Molecular dynamic simulation was used to analyze the tribological performance under pressure of 500 MPa, temperature 353 K, and shear velocity of 20 m/s; the volume compression and shear stress of lubricant films were obtained. Molecular volume, adsorption energies, radius of gyration, and mean square displacement were used to analyze the relationship between molecular structure and lubricant performance. Results show that the characteristic of the Iso and Mid type have the best friction reduction performance. The molecules of the Iso structure have the highest oil film thickness and the best load-bearing performance. The radius of gyration increases with the shear simulation for most of the molecules. The adsorption energy of End is the highest, and the Mid is the smallest. Among the nine molecules, C20Iso shows excellent performance both in load-bearing and friction reduction, which provides a reference for the molecular design of high-performance lubricant base oils. Full article

Background: Insect-derived proteins constitute an underutilized biological resource requiring urgent exploration to address global food protein shortages. However, their widespread application is hindered by the allergenic potential, particularly phospholipase A2 (PLA2), a highly immunoreactive allergen prevalent in edible insects such as ants and honeybees. Objective: This study systematically investigated the molecular mechanism underlying quercetin-mediated reduction in PLA2 allergenicity, aiming to establish a novel strategy for developing hypoallergenic insect protein resources. Methods and Results: Through integrated computational and experimental approaches, we identified quercetin’s dual non-covalent and covalent binding capabilities with PLA2. Molecular docking revealed robust interactions (the binding energy of −6.49 kcal/mol) within the catalytic pocket. Meanwhile, mass spectrometry specifically identified Cys37 as the covalent modification site, which can bind to quercetin and increase the gyration radius (Rg) of PLA2 within 75–125 ns. Molecular dynamics simulations illustrated quercetin-induced conformational changes affecting critical antigenic epitopes. Murine experiments further confirmed that quercetin-modified PLA2 exhibited significantly reduced IgE reactivity and allergic responses compared to native PLA2, as demonstrated by assessments of anaphylactic behavior, histopathological changes, and measurements of serum IgE antibody and biogenic amine levels. Conclusions: Collectively, these findings provide a transformative approach to safely utilize insect-derived proteins for sustainable nutrition solutions. Full article

Background: Human Metapneumovirus (HMPV) is a respiratory virus in the Pneumoviridae family. HMPV is an enveloped, negative-sense RNA virus encoding three surface proteins: SH, G, and F. The highly immunogenic fusion (F) protein is essential for viral entry and a key target for vaccine development. The F protein exists in two conformations: prefusion and postfusion. The prefusion form is highly immunogenic and considered a potent vaccine antigen. However, this conformation needs to be stabilized to improve its immunogenicity for effective vaccine development. Specific mutations are necessary to maintain the prefusion state and prevent it from changing to the postfusion form. Methods: In silico mutagenesis was performed on the C-terminal domain of the pre-F protein, focusing on five amino acids at positions 469 to 473 (LVDQS), using the established pre-F structure (PDB: 8W3Q) as the reference. The amino acid sequence was sequentially mutated based on hydrophobicity, resulting in mutants M1 (IIFLL), M2 (LLIVL), M3 (WWVLL), and M4 (YMWLL). Increasing hydrophobicity was found to enhance protein stability and structural rigidity. Results: Epitope mapping revealed that all mutants displayed significant B and T cell epitopes similar to the reference protein. The structure and stability of all mutants were analyzed using molecular dynamics simulations, free energy calculations, and secondary structure analysis. Based on the lowest RMSD, clash score, MolProbity value, stable radius of gyration, and low RMSF, the M1 mutant demonstrated superior structural stability. Conclusions: Our findings indicate that the M1 mutant of the pre-F protein could be the most stable and structurally accurate candidate for vaccine development against HMPV. Full article