Monitoring the Dynamics of Monomer Exchange Using Electrospray Mass Spectrometry: The Case of the Dimeric Glucosamine-6-Phosphate Synthase

Escherichia coli glucosamine-6-phosphate synthase (GlmS) is a dimeric enzyme from the glutamine-dependent amidotransferases family, which catalyses the conversion of D-fructose-6-phosphate (Fru6P) and glutamine (Gln) into D-glucosamine-6-phosphate (GlcN6P) and glutamate, respectively. Extensive X-ray crystallography investigations have been reported, highlighting the importance of the dimeric association to form the sugar active site as well as significant conformational changes of the protein upon substrate and product binding. In the present work, an approach based on time-resolved noncovalent mass spectrometry has been developed to study the dynamics of GlmS subunit exchange. Using ¹⁴N versus ¹⁵N labeled proteins, the kinetics of GlmS subunit exchange was monitored with the wild-type enzyme in the presence of different substrates and products as well as with the protein bearing a key amino acid mutation specially designed to weaken the dimer interface. Determination of rate constants of subunit exchange revealed important modifications of the protein dynamics: while glutamine, glutamate, and K603A mutation accelerates subunit exchange, Fru6P and GlcN6P totally prevent it. These results are described in light of the available structural information, providing additional useful data for both the characterization of GlmS catalytic process and the design of new GlmS inhibitors. Finally, time-resolved noncovalent MS can be proposed as an additional biophysical technique for real-time monitoring of protein dynamics.     

Modeling and numerical simulation of electrical and optical characteristics of a quantum dot light-emitting diode based on the hopping mobility model: Influence of quantum dot concentration

We present a comprehensive numerical framework for the electrical and optical modeling and simulation of hybrid quantum dot light-emitting diodes (QD-LEDs). We propose a model known as hopping mobility to calculate the carrier mobility in the emissive organic layer doped with quantum dots (QDs). To evaluate the ability of this model to describe the electrical characteristics of QD-LEDs, the measured data of a fabricated QD-LED with different concentrations of QDs in the emissive layer were taken, and the corresponding calculations were performed based on the proposed model. The simulation results indicate that the hopping mobility model can describe the concentration dependence of the electrical behavior of the device. Then, based on the continuity equation for singlet and triplet excitons, the exciton density profiles of the devices with different QD concentrations were extracted. Subsequently, the corresponding luminance characteristics of the devices were calculated, where the results are in good agreement with the experimental data.     

Preparation of silicon carbide film by a plasma focus device

Silicon carbide (SiC) films were grown on the silicon (100) substrate by a 20 kJ Mather-type dense plasma focus device. The preparation method and characterization data are presented. X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (SEM) and nano-indentor were employed for the characterization of the samples obtained at different axial position of 50 mm, 90 mm, 130 mm and 170 mm, respectively. Polycrystalline 3CSiC were obtained at the position of 90 mm and 130 mm from XRD and FTIR spectra. SEM image showed that the silicon carbide films obtained at the position of 90 mm are porous on surface layer. Nano-indentor indicates that the film obtained at the position of 130 mm has the highest mechanical hardness.     

Nontrivial tensile behavior of rutile TiO<Subscript>2</Subscript> nanowires: a molecular dynamics study

In this paper, we study the tensile behavior of cylindrical rutile TiO₂ nanowires, employing molecular dynamics (MD) simulation technique. The third-generation charge optimized many-body (COMB3) has been used for interatomic potential modeling. The influence of temperature and nanowire diameter on Young’s modulus is investigated. Our simulations exhibit the anisotropic behavior of Young’s modulus as a function of diameter for different crystallographic orientations. Although our results are in good accord with the existing results in [1 0 0] direction, Young’s modulus adds up monotonically with increasing the cross-sectional diameter of nanowire in [0 0 1] direction. It is found that Young’s modulus of the nanowires are lower (higher) than the bulk value for [0 0 1] ([1 0 0]) direction. Furthermore, simulation results also indicate that Young’s modulus of rutile TiO₂ nanowire increases as a function of temperature for a given diameter, unexpectedly. The obtained results may be useful in the field of nanotechnology for optimizing mechanical performance to gain specific applications.     

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.     

Diversification of a Novel α-Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines

The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α-galactosyl ceramide (α-GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B-cell activation. Herein, we introduce a novel derivatization hotspot at the α-GalCer skeleton, namely the N-substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self-adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen-specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α-GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α-GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.