The study intends to repurpose FDA drugs and investigate the mechanism of (5HT2BR) activation by comprehending inter-residue interactions. The 5HT2BR is a novel thread, and its role in reducing ...seizures in Dravet syndrome is emerging. The crystal structure (5HT2BR) is a chimera with mutations; hence 3D-structure is modeled (4IB4: 5HT2BRM). The structure is cross-validated to simulate the human receptor using enrichment analysis (ROC: 0.79) and SAVESv6.0. Virtual screening of 2456 approved drugs yielded the best hits that are subjected to MM/GBSA and molecular dynamic (MD) simulations. The 2 top drugs Cabergoline (−53.44 kcal/mol) and Methylergonovine (−40.42 kcal/mol), display strong binding affinity, and ADMET/SAR analysis also suggests their non-mutagenic or non-carcinogenic nature. Methylergonovine has a weaker binding affinity and lower potency than standards Ergotamine (agonist) and Methysergide (antagonist) due to its higher Ki (1.32 M) and Kd (6.44 ×10−8 M) values. Compared to standards, Cabergoline has moderate binding affinity and potency Ki = 0.85 M and Kd = 5.53 × 10–8 M. The top 2 drugs primarily interact with conserved residues (ASP135, LEU209, GLY221, ALA225, and THR140) as in agonists, unlike the antagonist. The top 2 drugs, upon binding to the 5HT2BRM, modify the helices VI, V, and III and shift the RMSD 2.48 Å and 3.07 Å. LEU209 forms a latch with residues 207–214 (forms a lid) in the 5HT2BRM receptor, which enhances agonist binding and prevents drug escape. Methylergonovine and Cabergoline interact more stongly with ALA225 than the antagonist. The post-MD analysis of Cabergoline suggests a better MM/GBSA value (−89.21 kcal/mol) than Methylergonovine (−63.54 kcal/mol). In this study, Cabergoline and Methylergonovine's agonistic mechanism and solid binding properties suggest their strong role in regulating the 5HT2BR and might target drug-resistant epilepsy.
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•Study investigates repurposing of FDA drugs for 5HT2BR activation and reducing seizures in Dravet syndrome.•Cabergoline and Methylergonovine show strong binding affinity and potential for regulating the 5HT2BR receptor.•Both drugs interact with conserved residues as in agonists, modifying specific helices upon binding.•LEU209 forms a latch in the receptor, enhancing agonist binding and preventing drug escape.•Cabergoline (−89.21 kcal/mol) shows better MM/GBSA value than Methylergonovine (−63.54 kcal/mol) post-MD analysis, suggesting stronger potential for targeting drug-resistant epilepsy.
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Hybrid solvents based on cholinium amino acid ionic liquids (ChAA ILs) mixed with water are environmentally benign solvents with low toxicity. ChAA ILs are used in biomass ...pretreatment processes to dissolve targeted (macro)molecules such as lignin from lingnocellulose. Understanding how ChAA ILs dissolve polymers is therefore of great interest for the rational design of ILs towards industrial application. Variation of the IL anion and the water concentration are hypothesised to change the solvent properties of ChAA hybrid solvents. Therefore, we probe the solvent quality of ChAA aqueous solutions with different anions (glycinate, prolinate and argininate) and water concentration for the simple model solute poly(ethylene glycol) (PEG).
Partial phase diagrams were produced to probe the salting-out effect of ChAA ILs towards PEG (Mw = 38 kDa). Small-angle neutron scattering experiments of deuterated PEG in hydrogenous ChAA aqueous solutions were performed to determine the polymer radius of gyration at infinite dilution (Rg,0) via Zimm-plots. Polymer concentration dependent apparent Rg values were obtained fitting an excluded volume polymer model onto the scattering data. Blends of hydrogenous and deuterated PEG under zero average contrast conditions were analysed to probe Rg at high polymer concentrations.
Hydrogen bond capacity of the anion is key to the salting-out effect of ChAA ILs on PEG. Rg,0 depends on anion species and water concentration. At IL:water = 1:30 (mole:mole) and 37 °C, cholinium argininate and cholinium glycinate are close to theta solvents while cholinium prolinate and dilute cholinium argininate (IL:water = 1:100) are between theta and good solvents.
The fabrication of high-quality low-fat 3D printed foods is strongly dependent on the development of shear-thinning, viscoelastic, and thixotropic ink with a monomodal particle size distribution. In ...this study, oil was partially or totally replaced with hydrophobically modified biosurfactants (acetylated starch, octenyl succinic anhydride starch, ethyl (hydroxyethyl) cellulose, and dodecenyl succinylated inulin) in a soy protein-based emulsion to produce the desired reduced-fat emulsion gels for potential applications in the 3D printing process. These reduced-fat emulsion gels exhibited pseudoplastic behavior with viscoelastic properties, where viscosity recovery, frequency crossover point, and storage modulus were found to increase with increasing biosurfactants ratio. Higher levels of surface-active biopolymers also yielded inks with lower creep compliance, a smaller droplet size having a more uniform distribution, and possessing improved structural strength and storage stability. Spherical droplets of inks with higher ratios of biosurfactants remained well dispersed. The differences in molecular weight and radius of gyration of biosurfactants accounted for the observed differences in flow behavior and emulsion stability, where inks including dodecenyl succinylated inulin and ethyl (hydroxyethyl) cellulose offered stable structures with strong gel-like properties compared to acetylated and octenyl succinic anhydride starches. All ink networks were also dynamic and recoverable, thus demonstrating the potential of these reduced-fat inks in 3D printing processes.
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•Biosurfactants with a higher value of intrinsic viscosity and radius of gyration offered a stable emulsion gel.•Elastic properties were more increased by biosurfactants with higher effective volume and molecular weight.•Biosurfactants increased creep-recovery percentages and provided a dynamic and recoverable ink system.•Fluorescence images displayed the droplets in the emulsions were present in separated and non-flocculated shapes.•The formation of shear-thinning, viscoelastic, and thixotropic inks by biosurfactants is promising for 3D printing.
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Depletion attraction induced by polymers can be employed across multiple disciplines. Previous studies implied that besides screening the electrostatic repulsion between colloids, ...adding salt may also affect the polymers even in a nonpolar solvent. Here, we study the depletion-induced gelation of a colloid-polymer model system, focusing on the salt effects on the depletion attraction.
Confocal microscopy was used to quantitatively characterize the colloidal gels formed by the polymethylmethacrylate (PMMA)/polystyrene (PS) model system. The attraction experienced by colloids was estimated by correlating the colloidal dynamics with the local structure. Correspondingly, static light scattering was employed to systematically investigate the polymers. The resulting radius of gyration Rg and osmotic pressure were used to evaluate the depletion attraction offered by polymers.
Salt was discovered to lower the strength of inter-particle attraction, which can be attributed to the salt-induced decrease in Rg. The depletion attraction grew sublinearly with c, owing to the considerable decrease in Rg in the good solvent as c increased. We demonstrated how the close form equations in the framework of renormalization group theory can be employed to predict the depletion interaction using the properly determined zero-concentration radius of gyration.
The injection of surfactant solutions into coal seams is one of the most critical technical means of preventing coal mine disasters. It can effectively prevent coal and gas outburst disasters by ...reducing the gas concentration at the coal mining face. The Wiser model of coal was utilized to establish the initial CH4-containing coal. Different concentrations (0%, 0.2%, 0.4%, 0.8%, 1.2%, and 1.6%) of alkyl poly glucoside surfactant (APG) were injected into CH4-containing coal to investigate the microkinetic mechanism of inhibiting gas desorption. The diffusion parameters of CH4 (i.e., diffusion coefficient, relative concentration, interaction radius), the gyration radius of APG, and the interaction energy between surfactant solution and CH4-containing coal were analyzed on the basis of the kinetic results. Results showed that with the increase in APG concentration, the diffusion coefficient of CH4 decreased gradually. The distribution of CH4 in coal molecules and the change rate of diffusion coefficient increased remarkably. When the concentration of APG was 0%, the diffusion coefficient was 12.00 × 10−7 m2 s−1, and that of 1.6% was 5.65 × 10−7 m2 s−1, a reduction of 52.91% compared with the concentration of 0%. With the increasing concentration of APG, the gyration radius increased, and the interaction energy between APG and CH4-containing coal molecules decreased. The CH4 diffusion coefficient was negatively correlated with the APG gyration radius, and the number of hydrogen bonds was positively correlated with the interaction energy. With the increase in the gyration radius of APG molecule, more hydrogen bonds were formed between APG surfactant and coal molecules, resulting in a decrease in the interaction energy. The system gradually stabilized to effectively inhibit the diffusion of CH4 in coal, which can provide a basis to prevent coal and gas outburst disasters.
•The desorption characteristics of CH4 under the influence of different concentrations of APG were investigated.•The mechanism of interaction between the moleculeswas investigated under different APG concentrations.•The radius of gyration of surfactant molecules influenced the diffusion coefficient of CH4.•The interaction energy of APG surfactant and CH4-containing coal decreases with increasing surfactant concentration.
Incipient soot particles obtained from a series of reactive molecular dynamics simulations were studied to understand the evolution of physical, chemical, and morphological properties of incipient ...soot. Reactive molecular dynamics simulations of acetylene pyrolysis were performed using ReaxFF potential at 1350, 1500, 1650, and 1800 K. A total of 3324 incipient soot particles were extracted from the simulations at various stages of development. Features such as the number of carbon and hydrogen atoms, number of ring structures, mass, C/H ratio, radius of gyration, surface area, volume, atomic fractal dimension, and density were calculated for each particle. The calculated values of density and C/H ratio matched well with experimental values reported in the literature. Based on the calculated features, the particles were classified in two types: type 1 and type 2 particles. It was found that type 1 particles show significant morphological evolution while type 2 particles undergo chemical restructuring without any significant morphological change. The particle volume was found to be well-correlated with the number of carbon atoms in both type 1 and type 2 particles, whereas surface area was found to be correlated with the number of carbon atoms only for type 1 particles. A correlation matrix comparing the level of correlation between any two features for both type 1 and type 2 particles was created. Finally, based on the calculated statistics, a set of correlations among various physical and morphological parameters of incipient soot was proposed.
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•Incipient soot particles grow from smaller (type 1) to larger and more spherical nanoparticles (type 2).•As incipient particles grow, the degree of correlations between various physico-chemical features changes.•Volume and surface area are found to be well-correlated with the mass of type 1 particles.•Type 2 particles show a prominent chemical reorganization with a noticeable increase in six-member rings at the expense of five- and seven-member rings.
Insight into the role of electrostatic interactions on the hydrodynamics and conformation of aqueous sodium alginate was gained through viscometry. Alginate chains are found to shrink in salt-free ...solutions more rapidly with increasing polymer concentration compared to salt-solutions. For salt-free solutions, a reduced polymer concentration of less than 1 suffices to make the alginate coil volume half of that at infinite dilution which becomes invariant when the reduced concentration exceeds 8. In saline media having salt concentration greater than 0.1 mol·L−1, the chains become more flexible, caused by the shielding of intra-chain repulsions. The chains effectively reached unperturbed state when the added salt concentration becomes ≥0.5 mol·L−1. Alginate chains are shown to remain stiff up to about 8–10 monomers within the investigated temperature range. This study explores the possible modification of the individual chain behavior induced by the neighboring chains or by the variation of temperature.
Several studies have revealed that the glass transition temperature (Tg) of polymer nanocomposites (PNCs) may change upon the loading of even a small number of nanoparticles (NPs). However, the exact ...phenomenon behind such shifting in Tg is still not well known. This study uses experimental and MD simulation approaches to explore the physics of the Tg of polyaniline (PANI) nanocomposite with molybdenum carbide (Mo2C) nanoparticles at different weight percentage loading of NPs. The experimental study shows that, at a lower wt-% loading of NPs, the Tg of the resulting PNCs decreases slowly, and above a particular loading wt-%* (30 wt-%), the depression in Tg becomes more serious. The SEM images show that for wt-% < wt-%*, NPs remain diffuse in the polymer matrix, and for wt-%t > wt-%* a large number of NPs surround the polymer. The MD simulation reveals a slow increase in the diffusion of polymer and NPs for wt-% < wt-%* and a sudden increase for wt-%t > wt-%*. The measurement of the radius of gyration of the polymer reveals swelling of the polymer for wt-% < wt-%* and contraction of the polymer for wt-%t > wt-%*. Moreover, the variations of the diffusion constants and the radius of gyration of the polymer are consistent with the Tg behaviour of PNCs.
Molecular dynamics (MD) simulations and complementary experiments are used here to understand the inter- and intramolecular structure and conformational properties of ionenes (i.e., cationic polymers ...formed from condensation reactions) dissolved in an ionic liquid (IL), 1-ethyl-3-methylimidazolium bistriflimide C2mim+Tf2N-. The simulated structural properties are benchmarked against experimental analyses of these same polymers, mainly using dynamic light scattering (DLS) experiments. Four different imidazolium ionenes are considered, corresponding to variations in the chemistry and structure of the repeat units including: (1) poly (decylimidazolium) (PD10); (2) poly (tetraethyleneglycolimidazolium) (PE10); (3) alternating copolymer (P(ED)5); and (4) a block copolymer (PE5D5). Detailed computational analyses of the polymer structure and conformational properties were performed, including the radius of gyration, end-to-end distance, torsional distributions, and site-site and spatial distribution functions. Overall, there is a competition between intramolecular associations between the imidazolium groups and the ether sites in the polymers versus the intermolecular interactions of the polymer imidazolium groups with the surrounding anion molecules. The polymer with only ether linkages (PE10) results in the most intramolecular interactions, leading to significant coiling behavior and chain contraction. These strong interactions reduce chain flexibility, but they also result in much more linear chain configurations and alignment of the imidazolium groups. The polymer structure is strongly affected as the concentration of alkyl groups is increased, and we find that the polymer architecture (alternating versus block copolymer) also has an important influence. Furthermore, these detailed observations are important for understanding the connection between the molecular design of imidazolium polymers and their emergent structural properties, which could lead to unique opportunities for creating polymer composites.
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•Prolines are much more enriched in IDPs than in folded proteins.•Often, high proline content in IDPs is expected to expand Rg via formation of PPII.•Proline can impose either ...compaction or expansion regardless of trans-cis switching.•This dual role of proline mostly depends on its organization patterns.•Introducing prolines as isolated or clustered improves prediction of IDPs dimension.
Intrinsically disordered proteins (IDPs) adopt a wide array of different conformations that can be constrained by the presence of proline residues, which are frequently found in IDPs. To assess the effects of proline, we designed a series of peptides that differ with respect to the number of prolines in the sequence and their organization. Using high-resolution atomistic molecular dynamics simulations, we found that accounting for whether the proline residues are clustered or isolated contributed significantly to explaining deviations in the experimentally-determined gyration radii of IDPs from the values expected based on the Flory scaling-law. By contrast, total proline content makes smaller contribution to explaining the effect of prolines on IDP conformation. Proline residues exhibit opposing effects depending on their organizational pattern in the IDP sequence. Clustered prolines (i.e., prolines with ≤2 intervening non-proline residues) result in expanded peptide conformations whereas isolated prolines (i.e., prolines with >2 intervening non-proline residues) impose compacted conformations. Clustered prolines were estimated to induce an expansion of ∼20% in IDP dimension (via formation of PPII structural elements) whereas isolated prolines were estimated to induce a compaction of ∼10% in IDP dimension (via the formation of backbone turns). This dual role of prolines provides a mechanism for conformational switching that does not rely on the kinetically much slower isomerization of cis proline to the trans form. Bioinformatic analysis demonstrates high populations of both isolated and clustered prolines and implementing them in coarse-grained molecular dynamics models illustrates that they improve the characterization of the conformational ensembles of IDPs.
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