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[Display omitted] Elucidation of the micro-mechanisms of sol–gel transition of gelling glucans with different glycosidic linkages is crucial for understanding their structure–property relationship and for various applications. Glucans with distinct molecular chain structures exhibit unique gelation behaviors. The disparate gelation phenomena observed in two methylated glucans, methylated (1,3)- β - d -glucan of curdlan (MECD) and methylated (1,4)- β - d -glucan of cellulose (MC), notwithstanding their equivalent degrees of substitution, are intricately linked to their unique molecular architectures and interactions between glucan and water. Density functional theory and molecular dynamics simulations focused on the electronic property distinctions between MECD and MC, alongside conformational variations during thermal gelation. Inline attenuated total reflection Fourier transform infrared spectroscopy tracked secondary structure alterations in MECD and MC. To corroborate the simulation results, additional analyses including circular dichroism, rheology, and micro-differential scanning calorimetry were performed. Despite having similar thermally induced gel networks, MECD and MC display distinct physical gelation patterns and molecular-level conformational changes during gelation. The network of MC gel was formed via a "coil-to-ring" transition, followed by ring stacking. In contrast, the MECD gel comprised compact irregular helices accompanied by notable volume shrinkage. These variations in gelation behavior are ascribed to heightened hydrophobic interactions and diminished hydrogen bonding in both systems upon heating, resulting in gelation. These findings provide valuable insights into the microstructural changes during gelation and the thermo-gelation mechanisms of structurally similar polysaccharides. [ABSTRACT FROM AUTHOR]

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure–property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P‐glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well. [ABSTRACT FROM AUTHOR]

Understanding the interaction between drugs and human serum albumin (HSA) is crucial for drug development. This study investigates the binding of a COVID‐19 drug, nirmatrelvir (NIR), to HSA through a computational approach. Molecular docking was employed to identify potential NIR binding site on HSA, and revealed distinct clusters at Sites I, II, and III. However, Site III exhibited a preference for NIR based on the lowest binding energy. Molecular dynamics simulation over 100 ns confirmed the stability of the NIR−HSA complex, with consistent binding at Site III. The compactness of HSA was maintained throughout the simulation period, as indicated by the radius of gyration, while structural flexibility analysis revealed typical fluctuations around some residues. Root‐mean‐square deviation (RMSD) patterns illustrated stability of the complex, and hydrogen bond analysis suggested four stable hydrogen bonds between NIR and HSA. These investigations offer insightful information on molecular interactions governing the stability of the NIR−HSA complex. [ABSTRACT FROM AUTHOR]

Introduction: Amorphous drug dispersion is frequently used to enhance the solubility and dissolution of poorly water-soluble drugs, thereby improving their oral bioavailability. The dispersion of these drugs into polymer matrix can inhibit their recrystallization. The inter-molecular interactions between drug and polymer plays a role in the improvement of the dissolution rate, solubility, and physical stability of drug.Aim: This study aims to investigate the formation and interactions of ritonavir (RTV)/poloxamer (PLX) amorphous formulation using a computational approach via molecular dynamics (MD) simulations, which mimicked solvent evaporation and melt-quenching method.Methods: TheRoot Mean Square Deviation (RMSD) value, Root Mean Square Fluctuation (RMSF), Radial Distribution Function (RDF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and hydrogen bond interactions were analyzed to determine interaction mechanisms between RTV and PLX in amorphous solid dispersion.Results: The pi-alkyl bonds between RTV and PLX were formed after simulations of solvent evaporation, while the hydrogen bond interactions of RTV-PLX was observed during melt method simulations. These results indicate the successful formulation of amorphous solid dispersion (ASD) from RTV and PLX. The RMSD values obtained from the solvent evaporation, melt-cooling-A, melt-cooling-B, and melt-cooling-C methods were 3.33 Å, 1.97 Å, 1.30 Å, and 1.29 Å, respectively, while the average RMSF values were 2.65 Å, 1.04 Å, 1.05 Å, and 1.07 Å, respectively. This indicates that the suppression of translational motion of RTV from the melt method can be stronger than solvent evaporation caused by the intermolecular interactions of RTV-PLX.Conclusion: MD simulations helped in understanding the formation and interaction mechanisms of ASD formulations that were difficult to detect by experimental approaches. [ABSTRACT FROM AUTHOR]

Die molekulardynamische Simulation ist eine weit verbreitete Methode, die Einblicke in die submikroskopische Ebene von Vielteilchensystemen erlaubt und die Berechnung makroskopischer und struktureller Eigenschaften ermöglicht. Sie kann auch didaktisch hilfreich zur Vermittlung von Wechselwirkungen und den daraus resultierenden molekularen Prozessen sein. Der Umgang mit der Frage, wie eine solche Simulation abläuft, kann zum Verständnis chemischer Inhalte beitragen. Dieses „Wie" erfordert eine Auseinandersetzung mit den Simulationsmethoden und den molekularen Modellen auf der Grundlage einsehbarer Programmcodes. Bei solchen Glass‐Box Simulationen ist der Code Teil der Behandlung chemischer Inhalte. Dabei wird informatisches Denken genutzt, um mit Algorithmen molekulare Vorgänge zu erläutern. In diesem Artikel werden die van der Waals‐Wechselwirkung, die Geschwindigkeitsverteilung sowie die Struktur von Fluiden und Feststoffen behandelt. Neben einer Visualisierung der submikroskopischen Prozesse ermöglicht dieser Ansatz auch Erkenntnisse über die Natur von Modellen. Hinzu kommt, dass Programmierfähigkeiten in den Naturwissenschaften von großer Bedeutung sind und auch im schulischen Bereich für die damit verbundenen Möglichkeiten sensibilisiert werden sollte. [ABSTRACT FROM AUTHOR]

Phytosterol, recognized for its health benefits, is predominantly extracted from plants and exhibits significantly reduced stability under varying light conditions. Their photooxidation is significantly influenced by emulsion interfaces. This study examined the mechanism of interface structure on phytosterol photooxidation with unparalleled molecular precision, utilizing molecular dynamics simulations and experimental procedures. Hydrogen bonding between the hydroxyl group at the C3 position of phytosterols and water molecules, coupled with van der Waals forces between the hydrophobic regions and the oil phase, induced phytosterol molecules to disperse toward the interface. The elevated polarity of the oil phase, specifically in tributyrin, facilitated the permeation of water molecules into the oil phase. This was achieved by diminishing the emulsion's interfacial tension, thereby fostering the development of more interface or micelles, and accelerating the photooxidation process of phytosterols. These simulations unraveled that the preponderance of phytosterol distribution is localized and oxidized at the oil-water interface. [Display omitted] • Molecular dynamic indicated phytosterols were located at O/W emulsion interface. • Phytosterols were impelled toward the interface through hydrogen bond with water. • Low polarity oil form more robust van der Waals force with phytosterols. • Polar oil molecules culminate in a less stable emulsion interface. • Oil pahse with higher viscosity ensnared phytosterols and reduce oxidation rate. [ABSTRACT FROM AUTHOR]

Insects stimulate specific behaviors by correctly recognizing scent molecules in the external environment. Sirex nitobei, a wood-boring wasp species native to Asia with a distribution area that includes the Palaearctic and Oriental regions, is a significant pest of conifers. Focusing on the molecular mechanism of protein-ligand binding, this study resolved the tissue expression profile of CSP4 from S. nitobei (SnitCSP4) and probed its binding properties with target ligands using molecular docking and dynamics simulations to verify the odor recognition function of this protein. The open reading frame (ORF) of SnitCSP4 was 396 bp, encoding 131 amino acids. Tissue expression analysis revealed that SnitCSP4 was significantly expressed in female antennae and docking showed that all ligands were bound in hydrophobic cavities and close to many hydrophobic amino acid residues. GLN68 and LEU49 were important amino acid residues for SnitCSP4 to bind various odors, and THR9 was the key ligand-binding site in identifying (-)-globulol in the SnitCSP4. Molecular dynamics verified the docking results, confirming that SnitCSP4 bound well to two sex pheromone molecules, three host plant volatiles, and three symbiotic fungal volatiles, with (Z)-7-heptacosene, (Z)-9-nonacosene, and (-)-globulol binding being the most highly stable. These results mean that SnitCSP4 is critical for insects recognizing scent molecules, providing a favorable molecular basis for regulating the behavioral interactions between S. nitobei and the environment, and offering the possibility of developing new strategies for more environmentally friendly and effective control. [ABSTRACT FROM AUTHOR]

The design of functional delivery systems is essential for storing and releasing active components. Inspired by the structure of Nepenthes mirabilis, cellulose nanocrystals (CNC) cooperate with cyclic α-cyclodextrins (α-CD), β-cyclodextrins (β-CD), and γ-cyclodextrins (γ-CD) to form nanocomposites at different mass ratios for the delivery the Mosla chinensis essential oils (EO)-loaded Pickering emulsions (PE), respectively. Characterization methods including FT-IR, TG, XPS, AFM, XRD, and three-phase contact angle were used to analyze the structure of the nanocomposites. The molecular docking and molecular dynamic simulation results revealed that the most hydrogen bonds were formed between β-CD and CNC, but the tendency for γ-CD and CNC to bond with hydrogen bonds was stronger in the molecular dynamic simulation. Subsequently, the physicochemical properties of emulsions stabilized by CNC/CDs nanocomposites were characterized through particle size, potential, microstructure, long-term stability, rheology, and aqueous phase distribution indexes. The results showed that the different mass ratios CNC/α-CD and CNC/β-CD nanocomposites stabilized PE had smaller droplet scales and better stability. While CNC/γ-CD nanocomposites had a negative effect on the emulsion. The in vitro release results showed that the emulsions stabilized by CNC/CDs nanocomposites had a slow-release rate for EO by diffusion. The simulated gastrointestinal release showed that CNC/β-CD-PE had the highest bioavailability. Moreover, CNC/β-CD-PE reduced the minimal inhibitory concentration of EO by a mechanism that disrupts the membrane structure of bacteria. Therefore, the introduction of β-CD may be an effective alternative in regulating the physical properties, function, and stabilization of CNC-based PE. These findings provide a scientific basis for the rational structural design of delivery systems for the encapsulated aroma molecules. [Display omitted] • Nepenthes mirabilis-inspired CNC/α, β, γ-CDs nanocomposites were prepared. • The interaction of CNC and CDs was explored by molecular dynamics simulation. • CNC/CDs nanocomposites on the behavior of Pickering emulsions were analyzed. • CNC/β-CD nanocomposites significantly improve PE stability and bioaccessibility. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hirshfeld surface analysis was firstly used to analysis the mechanism of DES and active substances. • Quantum chemistry and MD were used to analyze the mechanism of DES extraction of flavonoids and polyphenols. • Three active substances and six DESs were selected to analyze the selectivity during extraction. • HBD of hydroxyl group and short carbon chain showed advantages on the extraction of active substances. • Ethanolamine with both amino and hydroxyl groups had the best extraction effect. Choline chloride-based deep eutectic solvents (DES) have been demonstrated as promising green solvents for the extraction of flavonoids and polyphenols. This study investigates the interaction between six different hydrogen bond donors (HBD) choline chloride-based DES and three types of polyphenolic flavonoid substrates. Density functional theory (DFT) and molecular dynamics (MD) simulations suggest that Cl− dominates the interaction primarily through electrostatic forces. The extraction effect of alcohol DES on rutin was optimized obviously, and the maximum interaction could reach 737.6 kJ/mol. Acid DES has a better extraction effect on anthocyanins, with a maximum interaction of 376.4 kJ/mol. With the increase of the carbon chain of HBA and the increase of the number of functional groups, the interaction between DES and the active substance decreases. As HBD, ethanolamine with both hydroxyl and amino groups showed the best effect in the extraction process of DES, forming the maximum interaction energy of 1575.8 kJ/mol. Additionally, multivariate analysis is employed to establish the relationship between different variables and interaction energy. This study provides micro-theoretical support for the extraction of flavonoids and polyphenols. [ABSTRACT FROM AUTHOR]

[Display omitted] • The GROMACS molecular dynamics simulation software for food research is summarized. • The advantages and procedure of GROMACS for food research are summarized. • GROMACS provides valuable guidance for studying the properties of food molecules. • GROMACS can be used in food processing and food interaction. Food comprises proteins, lipids, sugars and various other molecules that constitute a multicomponent biological system. It is challenging to investigate microscopic changes in food systems solely by performing conventional experiments. Molecular dynamics (MD) simulation serves as a crucial bridge in addressing this research gap. The Groningen Machine for Chemical Simulations (GROMACS) is an open-source, high-performing molecular dynamics simulation software that plays a significant role in food science research owing to its high flexibility and powerful functionality; it has been used to explore the molecular conformations and the mechanisms of interaction between food molecules at the microcosmic level and to analyze their properties and functions. This review presents the workflow of the GROMACS software and emphasizes the recent developments and achievements in its applications in food science research, thus providing important theoretical guidance and technical support for obtaining an in-depth understanding of the properties and functions of food. [ABSTRACT FROM AUTHOR]

[Display omitted] The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development. [ABSTRACT FROM AUTHOR]

As a quarantine pest of conifer, Sirex noctilio has caused widespread harm around the world. It is expected that the molecular mechanism of protein–ligand binding can be elucidated to carry out the pest control. Through studies of SnocOBP12–ligand hydrophobic binding and dynamics and responsible amino acid residues identification, we got some promising results. SnocOBP12 had a general and excellent affinity for host plant volatiles, and may be a key protein for S. noctilio to find host plants. Among the many odor molecules that are bound to SnocOBP12, (−)-α-cedrene and (E)-β-farnesene from host plants and (−)-globuol from the symbiotic fungi of Sirex noctilio stood out and formed highly stable complexes with SnocOBP12. By the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method, the calculated free binding energy of the three complexes was −30.572 ± 0.101 kcal/mol, −28.349 ± 0.119 kcal/mol and −25.244 ± 0.152 kcal/mol, respectively. It was found that the van der Waals energy contributed to the stability of the complexes. Some key amino acid residues were also found: LEU74 and TYR109 were very important for SnocOBP12 to stably bind (−)-α-cedrene, while for (E)-β-farnesene, ILE6, MET10, and LEU74 were very important for the stable binding system. We discovered three potential ligands and analyzed the interaction pattern of the protein with them, this paper provides a favorable molecular basis for optimizing the attractant formulation. Investigation of the binding characteristics in the olfactory system at the molecular level is helpful to understand the behavior of S. noctilio and develop new methods for more effective and environmentally friendly pest control. [ABSTRACT FROM AUTHOR]

Insects stimulate specific behaviors by correctly recognizing scent molecules in the external environment. Sirex nitobei, a wood-boring wasp species native to Asia with a distribution area that includes the Palaearctic and Oriental regions, is a significant pest of conifers. Focusing on the molecular mechanism of protein-ligand binding, this study resolved the tissue expression profile of CSP4 from S. nitobei (SnitCSP4) and probed its binding properties with target ligands using molecular docking and dynamics simulations to verify the odor recognition function of this protein. The open reading frame (ORF) of SnitCSP4 was 396 bp, encoding 131 amino acids. Tissue expression analysis revealed that SnitCSP4 was significantly expressed in female antennae and docking showed that all ligands were bound in hydrophobic cavities and close to many hydrophobic amino acid residues. GLN68 and LEU49 were important amino acid residues for SnitCSP4 to bind various odors, and THR9 was the key ligand-binding site in identifying (-)-globulol in the SnitCSP4. Molecular dynamics verified the docking results, confirming that SnitCSP4 bound well to two sex pheromone molecules, three host plant volatiles, and three symbiotic fungal volatiles, with (Z)-7-heptacosene, (Z)-9-nonacosene, and (-)-globulol binding being the most highly stable. These results mean that SnitCSP4 is critical for insects recognizing scent molecules, providing a favorable molecular basis for regulating the behavioral interactions between S. nitobei and the environment, and offering the possibility of developing new strategies for more environmentally friendly and effective control.

The dielectric dispersion spectra of morpholine with methanol and ethanol binary mixtures have been studied by using Time Domain Reflectometry. Frequency dependent variations of specified mole fraction for the temperature 288 K, 293 K, 298 K, 303 K were determined. The complex permittivity spectra fitted by Debye model. The dielectric parameters of the associating liquids analysed and the ordering of molecules favours two relaxation sites and discussed on the basis of dielectric properties. The swapping bond of H at N–H favours intermolecular interaction. The intra-molecular exists between O and N within the ring. The excess properties of the mixture solutions has effective Kirkwood correlation factor that predicts molecular interaction and orientation among solute and solvents. The thermodynamic parameters ΔG, ΔH and ΔS of the solutions and dielectric loss factor of the mixed solvents bearing alcohols were determined. FTIR spectral assignments of solutions validate the molecular interaction and their shifts. [ABSTRACT FROM AUTHOR]

As a quarantine pest of conifer, Sirex noctilio has caused widespread harm around the world. It is expected that the molecular mechanism of protein–ligand binding can be elucidated to carry out the pest control. Through studies of SnocOBP12–ligand hydrophobic binding and dynamics and responsible amino acid residues identification, we got some promising results. SnocOBP12 had a general and excellent affinity for host plant volatiles, and may be a key protein for S. noctilio to find host plants. Among the many odor molecules that are bound to SnocOBP12, (−)-α-cedrene and (E)-β-farnesene from host plants and (−)-globuol from the symbiotic fungi of Sirex noctilio stood out and formed highly stable complexes with SnocOBP12. By the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method, the calculated free binding energy of the three complexes was −30.572 ± 0.101 kcal/mol, −28.349 ± 0.119 kcal/mol and −25.244 ± 0.152 kcal/mol, respectively. It was found that the van der Waals energy contributed to the stability of the complexes. Some key amino acid residues were also found: LEU74 and TYR109 were very important for SnocOBP12 to stably bind (−)-α-cedrene, while for (E)-β-farnesene, ILE6, MET10, and LEU74 were very important for the stable binding system. We discovered three potential ligands and analyzed the interaction pattern of the protein with them, this paper provides a favorable molecular basis for optimizing the attractant formulation. Investigation of the binding characteristics in the olfactory system at the molecular level is helpful to understand the behavior of S. noctilio and develop new methods for more effective and environmentally friendly pest control.

Molecular dynamic (MD) simulation is an approach frequently employed in computational biology for exhaustive sampling of the protein-ligand conformational space. Hence, it is useful for structural analysis and the study of molecular interactions. In this study, we report on a MD simulation protocol to understand the dynamics of β-secretase 1 [BACE1] and 2 [BACE2], widely known to play a critical role in the etiology of Alzheimer’s disease, by a structure change evaluation of their transmembrane domains while inserted in a simulated neural membrane system. We considered two different levels in membrane cholesterol content. Because there is no evidence supporting the capacity of BACE1 and BACE2 to exist as adimer, single and double [BACE1/BACE1, BACE2/BACE2, BACE1/BACE2] systems, either in parallel or antiparallel orientation, were prepared for each run. Analysis of tridimensional structure of BACE1 and BACE2, after 10ns of MD simulation, revealed a correlation between higher cholesterol levels and both peptide refolding and changes in the secondary structure of both transmembrane domains in single and double systems. Interestingly, our results also indicate a potential interaction in the double system BACE2/BACE2, particularly when the domains had an antiparallel orientation. [ABSTRACT FROM AUTHOR]

β -Glucuronidase plays a vital role in the metabolism of drugs and endogenous substance. Herein, we assayed the inhibitory effects of thirty-six flavonoids (1–36) toward β -glucuronidase (Escherichia coli) using the probe reaction of DDAO-glu hydrolysis. The results showed that kushenol X (6), (2 S)-farrerol (10), 5,7,2′-trihydroxy-8,6′-dimethoxy flavone (20), demethylbellidifolin (31), and gentisin (32) exhibited potent inhibitory activities toward β -glucuronidase with the IC 50 values of 2.07 ± 0.26, 8.95 ± 0.74, 4.97 ± 0.61, 0.91 ± 0.11, and 0.68 ± 0.10 μM, respectively. Furthermore, the inhibition kinetics studies indicated that demethylbellidifolin (31) and gentisin (32) exhibited mixed-type inhibiton toward β -glucuronidase, the K i values were caculated to be 4.05 and 2.02 μM, respectively. Additionally, the circular change of dichroism (CD) spectrum verified the interaction between demethylbellidifolin (31) and gentisin (32) with β -glucuronidase; following by the molecular docking and molecular dynamics further revealed the potential interaction amino acid site in β -glucuronidase. All our findings not only developed some potent novel β -glucuronidase inhibitors but also indicated the potential herb drug interaction (HDI) effects of flavonoids with some clinical drugs which had enterohepatic circulation and further revealed the vital pharamcophoric requirement of natural flavonoids for β -glucuronidase inhibition activity. • The inhibitory effects of 36 kind nature flavonoids toward β -Glucuronidase were assayed; • The mixed-type inhibition behaviour and inhibition parameter was illustrated and obtained by inhibition kinetics; • The potential interaction between flavonoids and β -Glucuronidase were illustrated by molecular docking and dynamics; [ABSTRACT FROM AUTHOR]

Molecular interaction between hydrogen molecules and B2H4M (M=Li, Be, Sc, Ti, V) complexes has been studied using the DFT method (M06 functional) and 6-311++G** basis set. The hydrogen uptake capacity of the complexes considered is higher than the target set by the US Department of Energy (5.5 wt% by 2020). The metal atom bound strongly to the B2H4 substrate. Adsorption of molecular hydrogen on Be-, Ti-, and V-decorated complexes is thermodynamically possible for all the pressures and temperatures considered whereas it is unfavorable for Li-decorated complexes for all the pressure and temperatures. For the Sc-doped complexes, adsorption of molecular hydrogen is favorable below 330 K and entire pressure range considered. All the H2 adsorbed complexes are kinetically stable. For all the complexes, the interaction between the inorganometallic complexes and the H2 molecules adsorbed is attractive whereas that between adsorbed H2 molecules is repulsive. We have also performed molecular dynamics simulations to confirm the same number of H2 molecule adsorption from the simulations and DFT calculations. [ABSTRACT FROM AUTHOR]

[Display omitted] • C3G has higher binding affinity to BLF/OTF at pH 7 than at pH 3 and 5. • Hydrophobic interactions and hydrogen bonds are primary driving forces. • Electrostatic attraction occurs only at pH 7 for the negatively charged C3G forms. • The stable protein structures at pH 7 favor the stabilization of C3G binding sites. The potential binding of cyanidin-3-O-glucoside (C3G) to bovine lactoferrin (BLF) and ovotransferrin (OTF) at pH 3, 5, and 7 was investigated for the first time. Multiple spectroscopic techniques demonstrated pH-dependent alterations in the conformational characteristics of BLF and OTF upon complexation with C3G. Fluorescence quenching assays showed that their highest binding affinity was at pH 7. Hydrophobic interactions and hydrogen bonds were found to be crucial in molecular dynamics simulations but with significantly lower probabilities of formation at pH 3 (p < 0.05). At pH 7, electrostatic attraction can occur for the negatively charged forms of C3G, and the well-maintained native structures of BLF and OTF may be favorable for stabilizing the C3G binding sites. This study sheds light on the stronger interaction of C3G with BLF/OTF at pH 7, which may have implications for future applications such as anthocyanin stabilization or the development of functional food ingredients. [ABSTRACT FROM AUTHOR]

(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called “closed conformation„, comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF.

This research study aimed to develop a new strategy for using a polymer blend in solid dispersion (SD) for dissolution enhancement of poorly water-soluble drugs. SDs with different blends of hydrophilic-hydrophobic polymers (zein/hydroxypropyl methylcellulose – zein/HPMC) were prepared using spray drying to modulate the drug crystal and polymer-drug interactions in SDs. Physicochemical characterizations, including power X-ray diffraction and Fourier transform infrared spectroscopy, were performed to elucidate the roles of the blends in SDs. Although hydrophobic polymers played a key role in changing the model drug from a crystal to an amorphous state, the dissolution rate was limited due to the wetting property. Fortunately, the hydrophilic-hydrophobic blend not only reduced the drug crystallinity but also resulted in a hydrogen bonding interaction between the drugs and the polymer for a dissolution rate improvement. This work may contribute to a new generation of solid dispersion using a blend of hydrophilic-hydrophobic polymers for an effective dissolution enhancement of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein-protein or protein-ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin- 1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. [ABSTRACT FROM AUTHOR]

This study investigates the molecular mechanism of used oil on improving the compatibility and viscosity reduction of rubberized asphalt (RA) using molecular simulations and lab tests. This validates the feasibility of producing waste oil modified RA while enhancing the sustainable use of resources and pavement performance. The model of RA with used oil was first built by Materials Studio software. Several molecular dynamics parameters were used to explore the molecular behavior, stability and viscosity of asphalt. Furthermore, the relevant experiments were employed to validate the results of molecular simulation. The results show that used oil molecules can promote the dispersion of macromolecules, including asphaltenes, resins and rubbers, making the system more in accord with the asphalt colloid theory. It supplements the light components in the system to provide a stable dispersion medium. FTIR spectra confirm the rubber activation with used oil and microwave radiation. The softening point difference of RA was reduced from 1.9 to 0.35 °C. Viscosity was even reduced by approximately 67.1%. [Display omitted] [ABSTRACT FROM AUTHOR]

Many cellular functions depend on highly specific intermolecular interactions, for example transcription factors and their DNA binding sites, microRNAs and their RNA binding sites, the interfaces between heterodimeric protein molecules, the stems in RNA molecules, and kinases and their response regulators in signaltransduction systems. Despite the need for complementarity between interacting partners, such pairwise systems seem to be capable of high levels of evolutionary divergence, even when subject to strong selection. Such behavior is a consequence of the diminishing advantages of increasing binding affinity between partners, the multiplicity of evolutionary pathways between selectively equivalent alternatives, and the stochastic nature of evolutionary processes. Because mutation pressure toward reduced affinity conflicts with selective pressure for greater interaction, situations can arise in which the expected distribution of the degree of matching between interacting partners is bimodal, even in the face of constant selection. Although biomolecules with larger numbers of interacting partners are subject to increased levels of evolutionary conservation, their more numerous partners need not converge on a single sequence motif or be increasingly constrained in more complex systems. These results suggest that most phylogenetic differences in the sequences of binding interfaces are not the result of adaptive fine tuning but a simple consequence of random genetic drift. [ABSTRACT FROM AUTHOR]

• The solubility of 4-chlorobenzophenone in different pure solvents was determined. • Several thermodynamic models were used to correlate the solubility data. • Dissolution thermodynamics of 4-chlorobenzophenone in different solvents were calculated. • The effects of solvent polarity and Hansen solubility parameters on solubility were discussed. • DFT calculation was explored to reveal the molecular interaction. Equilibrium mole fraction solubility of 4-chlorobenzophenone in eleven organic solvents, as well as in neat water, was determined at temperatures ranging from 278.15 K to 323.15 K. Solubility of 4-chlorobenzophenone in these solvents increased with rising of temperatures, and the data was adequately correlated with several well-known thermodynamic models with the average relative deviations (100 ARD) of 0.03 to 12.91%, suggesting good correlation. The effects of solvent polarity on solubility were also investigated, and 4-chlorobenzophenone dissolved more in less polar solvents (ester solvents) than in strong polar solvents (alcohol solvents) due to the weak polarity functional groups of 4-chlorobenzophenone. Respective apparent thermodynamic functions, i.e. Gibbs energy, enthalpy, and entropy, for the dissolution process, were calculated using the Wilson equation. Results showed that the dissolution process of 4-chlorobenzophenone was endothermic and spontaneous. Furthermore, Hansen solubility parameters (HSPs) were applied to further discuss the miscibility of 4-chlorobenzophenone in the selected solvents. Molecular dynamics simulation explored the molecular interaction between 4-chlorobenzophenone and solvents, and strong interaction between 4-chlorobenzophenone and ester solvents contributed to the higher solubility. [ABSTRACT FROM AUTHOR]

[Display omitted] • Heavy components have a strong affinity towards organic surfaces and water has a strong affinity towards clay surfaces. • Polar constituents of asphaltene/resin also show an affinity towards clay surfaces due to electrostatic interactions. • Presence of asphaltenes can expect to create modified wettability that will impact oil transport and distribution. • Water forms structures bridging between opposing surfaces of the clay model in addition to presence of any absorbed film. • This study is the first that considers water and multicomponent hydrocarbon mixtures in mixed-wet shale pores. Mixed wet pores are abundant in shales, yet there is little to no information on the behavior of fluids confined within pores characterized by one hydrophilic and one hydrophobic surface. This mixed wettability can impact fluid storage, distribution, capillary pressures and transport. In this study, we use molecular dynamics simulations to describe the initial distribution of reservoir fluids, such as multicomponent hydrocarbon mixtures and water, in mixed-wet pores. This is an essential pre-requisite to additional studies documenting fluid transport in such pores. The molecular model of the mixed wet pore used consists of kerogen separated by some distance from two clay surfaces. We evaluate spatial distribution of water and individual hydrocarbon species, at varying values of water concentration. Throughout the entire study, the results from the equilibrated system indicate a high affinity between the heavy components, such as the asphaltene/resin fraction and the kerogen surfaces. The more surprising result is the hydrogen bonding observed between the polar constituents in the asphaltene/resin fraction and water. This creates a situation where the asphaltene/resin fraction shows an affinity towards water. When this happens, the hydrophilic clay surface effectively becomes hydrophobic. A pore bounded by an asphaltene layer on one side and kerogen on the other is more oil-wetting than mixed-wet. The presence of asphaltenes can therefore expect to create conditions of modified wettability that will impact oil recovery, oil transport and distribution. Another surprising result in this work is that water forms structures that bridge between opposing surfaces of the model. These water bridges are seen to happen for water concentration values larger than 20%. In other words, water is not merely just adsorbed on to the clay surfaces, but also forms these bridge-like structures. Nevertheless, we still observe a strong affinity between the asphaltene/resin fraction and water leading to a lesser degree of mixed wettability. This study is the first, to the best of our knowledge, that considers water and multicomponent hydrocarbon mixtures in mixed-wet pores with realistic surface chemistry and constitutes a necessary first step towards additional studies related to water and hydrocarbon transport and EOR processes in shale nanopores. [ABSTRACT FROM AUTHOR]

Three β-chitin structures [anhydrous, di-hydrate, mono-ethylenediamine (EDA)] recently determined by synchrotron X-ray and neutron fiber diffraction were reviewed from the viewpoint of molecular interactions. Both water and EDA molecules interact with the chitin chains through multiple hydrogen bonds. When water complexes with chitin, the hydrogen bonding pattern rearranges with the replacement of an intrachain chitin hydrogen bond by a stronger hydrogen bond between chitin and water, with an associated reduction in the degrees of freedom; the water oxygen is a much stronger acceptor than the O5 ring atom. The behavior of hydrogen exchange by deuterium supports this interpretation. EDA-molecules change the conformation of hydroxymethyl group from gg to gt, accompanied by changes in hydrogen bonds due to the strong accepting ability of the EDA nitrogen atoms. Some important interactions are in common with experimental crystallographic results of cellulosic crystals and of molecular dynamics studies. These new insights into solid-solvent interactions are valuable in understanding molecular interactions in other polysaccharides-solvents system in solution or on surface. [ABSTRACT FROM AUTHOR]

[Display omitted] • The method of molecular dynamics simulation combined with experiment was adopted. • The natural polymer material locust bean gum is selected as the main material. • Analyzed the molecular electrostatic potential and hydrogen bond of the system. • Study the wetting mechanism of coal dust at the molecular level. To solve the problem of coal dust pollution, this paper used experiments and molecular dynamics simulations to develop a new composite dust suppressant with locust bean gum as the binder, fatty alcohol polyoxyethylene ether as the wetting agent, and glycerol as the water-retaining agent. Through a single factor analysis of the effects of each material, the appropriate concentrations of each were selected for an orthogonal experiment. The best composition of dust suppressant was obtained from an anti-wind erosion experiment. Then, scanning electron microscopy and energy-dispersive X-ray spectroscopy were performed on a coal sample sprayed with dust suppressant to observe that the dust suppressant had good adsorption on and binding to low-rank coal. Finally, an on-site experiment was conducted on the developed composite dust suppressant. The dust reduction rate reached 92.3%. Materials Studio software was used to simulate the interaction between dust suppressants and coal dust, with pure water as a control group for comparison. By analyzing the electrostatic potential of the dust suppressant and low-rank coal molecules, as well as the relative concentration distribution curves of both molecules, the water molecule mobility, and the heat of adsorption, the micro-action between dust suppressants and coal could be understood. [ABSTRACT FROM AUTHOR]

Abstract: Intra and intermolecular interactions between the components in the mixture of anisole and isobutanol and their concentration and temperature dependence have been reported using dielectric relaxation and viscometric studies. Permittivity and dielectric loss of the samples are determined by using microwave bench and they are used to calculate the relaxation time using Higasi and Cole–Cole models. Activation free energies, change in enthalpy and entropy due to both relaxation mechanism and viscous forces have been calculated. At all studied temperatures, positive values of enthalpy are obtained for the entire range of concentration studied whereas negative values of entropy are found to exist for maximum of concentrations. Investigation shows that the dielectric parameters vary with variation in temperature and concentration. Variations of the dielectric parameters are interpreted as per the available theory. [ABSTRACT FROM AUTHOR]

Abstract: We have used high-speed atomic force microscopy to study the dynamics of bacteriorhodopsin (bR) molecules at the free interface of the crystalline phase that occurs naturally in purple membrane. Our results reveal temporal fluctuations at the crystal edges arising from the association and dissociation of bR molecules, most predominantly pre-formed trimers. Analysis of the dissociation kinetics yields an estimate of the inter–trimer single-bond energy of −0.9kcal/mol. Rotational motion of individual bound trimers indicates that the inter–trimer bond involves W10–W12 tryptophan residues. [Copyright &y& Elsevier]

In spite of the ease of computing the Lennard-Jones function for describing van der Waals energy of interaction, the Exponential-6 function is normally adopted due to its better description of short range interaction. Hence scaling factors of 13.772 and 12 have been used to give equal curvature at the minimum well-depth and equal long-range energy description, respectively, when compared to the Lennard-Jones (12-6) potential. This paper proposes an intermediate scaling factor of 12.6533 on the basis of zero integral error from the well-depth to infinite separation. It is herein shown that the use of this intermediate scaling factor divides the entire Exponential-6 computation into three stages instead of two, thereby smoothening the energy curve by reducing the computed energy drop at the scaling factor switching point. In cases where a single scaling factor is desired as a results highly complex dynamical molecular system, the proposed intermediate scaling factor gives significantly smaller overall error. [ABSTRACT FROM AUTHOR]

Although small water clusters (SWCs) are important in many research fields, efficient methods of preparing SWCs are still rarely reported, which is mainly due to the lack of related materials and understanding of the molecular interaction mechanisms. In this study, a series of functional molecules were added in water to obtain small water cluster systems. The decreasing rate of the half-peak width in a sodium dodecyl sulfate (SDS)–water system reaches ≈20% at 0.05 mM from 17O nuclear magnetic resonance (NMR) results. Based on density functional theory (DFT) and molecular dynamics (MD) simulation calculation, it can be concluded that functional molecules with stronger negative electrostatic potential (ESP) and higher hydrophilicity have a stronger ability to destroy big water clusters. Notably, the concentrations of our selected molecule systems are one to two magnitudes lower than that of previous reports. This study provides a promising way to optimize aqueous systems in various fields such as oilfield development, protein stability, and metal anti-corrosion. [ABSTRACT FROM AUTHOR]

Experimental and molecular dynamics simulation study was used to clarify the hydrophilicity of substrate surfaces and hydrophobicity of as-prepared surfaces at molecular level. First, an easy one-step approach was utilized to construct superhydrophobic surfaces on different substrates such as steel, aluminum, glass, and silicon wafer. The superhydrophobicity of as-prepared surfaces were contributed to the fluorinated compositions and microstructures. A fluorinated surface was constructed as a model of the as-prepared superhydrophobic surface. Molecular dynamics simulations were utilized to elucidate the anti-wetting mechanism of as-prepared fluorinated surfaces on aluminum substrates. Compared with the compact hydrated layer on the aluminum substrate, the hydrated layer on the fluorinated surface were broader with a lower intensity, confirming the lower attractive force between surface and water molecules. The decreased van der Waals interaction with water molecules contributed to the hydrophobicity of the fluorinated surface. While, in an alkaline solution, the electrostatic interaction had a negative impact on hydrophobicity of a fluorinated surface. [Display omitted] • Superhydrophobic surfaces on different materials were fabricated by an easy one-step process. • The decreased van der Waals interaction with water molecules resulted in hydrophobicity. • MD simulations elucidated anti-wetting mechanism of superhydrophobic surfaces towards acid and alkaline solutions. • The electrostatic interaction weakened hydrophobicity of a fluorinated surface in an alkaline solution. [ABSTRACT FROM AUTHOR]

Structural characteristics, interfacial distribution and molecular interactions of the components of the CO 2 (gas)/SDS/water/SDS/CO 2 (gas) systems as a function of the CO 2 (gas)/water interface coverage by the SDS surfactant to different amounts of the CO 2 were studied with molecular dynamics simulations and the NVT ensemble. Initially, the repulsive nonbonding parameter between the water oxygen and CO 2 oxygen was adjusted to improve the prediction of the solvation free energy, solubility of the CO 2 gas in water and the behavior of the CO 2 (gas)/SDS/water/SDS/CO 2 (gas) systems at molecular level. Our results show that the stability of the studied foams can be improved incrementing of the vapor/water interface coverage with the SDS surfactant and the amount of CO 2 in the system. With the highest interface coverage, the sulfate group has a molecular array more compact at the interface. Furthermore, CO 2 gas have a reduction of the diffusion across of the hydrocarbon chains to the water layer with an increment of the number of CO 2 molecules in the system, indicating a behavior more hydrophobic of the CO 2 gas. The tendencies obtained of the simulations are consistent with the reported experimental results. [ABSTRACT FROM AUTHOR]

(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called "closed conformation", comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF. [ABSTRACT FROM AUTHOR]