A highly sensitive and selective E-DNA biosensor was fabricated on a gold substrate using a reduced graphene oxide/polypyrrole/gold nanoparticle/oligonucleotide (RGO/PPy/Au*NPs/Apt) nanocomposite ...electrode to detect the nucleocapsid protein of SARS-CoV-2 in the patient blood plasma. The modified electrode was characterized by physicochemical techniques such as Fourier transform-infra red (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS) analyses, Brunauer-Emmett-Teller (BET), and Barrett-Joyner-Halenda (BJH) analyses. Moreover, electrochemical analyses were employed to study the electrochemical performance of the electrodes including cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and square wave voltammetry (SWV). Computational investigations of N protein bindings such as hydrogen bonding, Van der Waals binding, and Gibbs binding energies of the N-protein, and aptamer were studied by Molecular Dynamics Simulations (MDS). The unique synergistic effect of RGO, PPy, and the well-known effect of Au nanoparticles makes the DNA probe immobilized on the gold electrode surface. After optimizing the systems, the E-DNA biosensor exhibited a fast SWV response, higher sensitivity (33.77 μA.nM−1.cm−2) and selectivity, high efficiency, good storage stability, and acceptable repeatability for monitoring DNA. The results of real samples based on SWV indicated the correct functioning of the aptasensor in the presence of the SARS-CoV-2 virus. The limit of detection was 3.16×10−17 M and the limit of quantitation was 1.42×10−16 M. The MDS results indicated the stable dynamic folding of the aptamer for beneficial binding. The results indicated that the RGO/PPy/Au*NPs/Apt biosensor is promising for detecting of SARS-CoV-2 virus.
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•E-DNA biosensor based on RGO/PPy/Au*NPs was fabricated.•The biosensor was used to detect the N-protein of SARS–CoV–2 in the real samples.•LOD, LOQ, and sensitivity were 3.16×10−17, 1.42×10−16 M, and 33.77 μA.nM−1.cm−2.•Computational investigations of N protein bindings were studied by MD simulations.•The binding interactions of the N-protein and aptamer were studied by MDs.
Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors activated by glutamate. A series of 90 novel compounds have been assessed as mGluR5 receptor antagonists. These compounds, ...selected post-ADMET filtering according to Lipinski's rule of five, represent structurally innovative ligands inspired by promising existing ones. Utilizing the FlexX program, the ligands were docked alongside the reference compound SIB1757 to mGluR5. Docking simulations unveiled compound 14, featuring an ortho-substituted moiety, as the most promising with a binding affinity of -47 kcal/mol, followed by compound 8 at -41 kcal/mol. A total of 31 docked molecules exhibited superior binding affinity compared to reference compounds. Subsequent molecular dynamics simulations over 100 ns confirmed the stability of protein-ligand complexes, establishing the efficacy of the selected compounds as negative allosteric modulators of mGluR5.G
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Overexpression or gene mutation of SHP2 is closely linked with a variety of cancers and has been identified as a crucial anticancer target. In the study, we took SHP2 allosteric inhibitor SHP099 as ...the lead compound, and 32 1,3,4-thiadiazole derivatives were identified as selective allosteric inhibitors of SHP2. In vitro enzyme activity test showed that some compounds had high inhibition on full length SHP2, and almost no activity on homologous protein SHP1, exhibiting high selectivity. Compound YF704 (4w) had the best inhibition activity, with IC50 value of 0.25 ± 0.02 μM, and also showed strong inhibitory activity on SHP2-E76K and SHP2-E76A, with IC50 values of 6.88 ± 0.69 μM and 1.38 ± 0.12 μM, respectively. CCK8 proliferation test found that multiple compounds would effectively inhibit the proliferation of a variety of cancer cells. Among them, the IC50 values of compound YF704 on MV4-11 and NCI–H358 cells were 3.85 ± 0.34 μM and 12.01 ± 0.62 μM, respectively. Specially, these compounds were sensitive to NCI–H358 cells containing KRASG12C mutation, thus overcoming the problem that SHP099 was insensitive to such cells. Apoptosis experiment showed that compound YF704 would effectively induce apoptosis of MV4-11 cells. Western blot showed that compound YF704 would downregulate the phosphorylation levels of Erk1/2 and Akt in MV4-11 and NCI–H358 cells. Molecular docking study show that compound YF704 would effectively bind to the allosteric region of SHP2 and form hydrogen bond interactions with key residues Thr108, Arg111 and Phe113. Molecular dynamics study further revealed the binding mechanism of SHP2 and compound YF704. In conclusion, we hope to provide potential SHP2 selective inhibitors and provide valuable clues for cancer treatment.
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•A class of 1,3,4-thiadiazole derivatives were first reported as SHP2 allosteric inhibitors.•Compound YF704 has a high inhibitory effect on both SHP2-E76K and SHP2-E76A mutants.•Compound YF704 can downregulate changes in signaling pathways in NCI–H358 cells.•The binding mechanism between YF704 and SHP2 was elucidated through MD simulation.
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•The pKa and pKa* of a photoacid 6-cyano-2-naphthol increases within α-CD while decreases within β-CD.•The ESPT dynamics is suppressed significantly within α-CD but almost unaltered ...within β-CD complex.•The photoacid forms 1:2 inclusion complex with α-CD, whereas 1:1 inclusion complex with β-CD.•The hydroxyl group of the photoacid has much lesser access to water inside the α-CD complex compared to the β-CD complex.
Herein, we investigate the interaction between a strong photoacid 6-cyano-2-naphthol (6CN-2OH) and a macrocyclic host α- cyclodextrin (α-CD) with a combination of molecular fluorescence and molecular dynamics simulations. Interestingly, we observe very different pKa shift and fluorescence modulation within α-CD compared to β- cyclodextrin (β-CD). While β-CD inclusion lowers pKa and pKa* of 6CN-2OH, α-CD inclusion raises them. Moreover, in contrast to negligible fluorescence change in the β-CD inclusion case, we observe a remarkable fluorescence modulation for the α-CD-inclusion case. Fluorescence transient measurements confirm significant suppression of excited-state proton transfer (ESPT) dynamics in the presence of α-CD but almost none for the β-CD complex. Isothermal calorimetry (ITC) measurements reveal that 6CN-2OH forms a 1:1 inclusion complex with β-CD with a moderate binding constant of 580 M−1; whereas it forms a 1:2 inclusion complex with α-CD with a high binding constant of 5.0 × 104 M−2. Fluorescence anisotropy decay measurements also support the different binding stoichiometry of the photoacid with the two CDs; the rotational relaxation is significantly slower in the α-CD complex than in the β-CD. Molecular dynamics simulation shows that 6CN-2OH remains entirely trapped inside the hydrophobic cavity formed by two α -CD molecules, which results in the severe depletion of water molecules from the proton-donating hydroxyl site of the 6CN-2OH molecule in the 6CN-2OH:(α-CD)2 complex than in the 6CN-2OH:β-CD complex.
•As CO2 pressure increases, kerogen wettability shifts from H2O-wet to CO2-wet.•CO2 crowding near kerogen surface at high CO2 pressures leads to the CO2-wet state.•Carbon skeleton favors CO2, ...resulting in a CO2 film formed at H2O-kerogen interface.
Geological CO2 sequestration (GCS) is an essential building block of the global strategy to alleviate greenhouse gas emissions and mitigate the climate change. Injecting CO2 into the shale formations can not only reduce carbon emissions but also enhance oil recovery (EOR). Rock wettability is of great importance to CO2 storage as it determines the efficiency of structural and residual trapping of CO2 and plays a crucial role in CO2-EOR. In this work, molecular dynamics (MD) simulations are adopted to investigate the CO2-H2O-kerogen systems under various CO2 pressures. In a vacuum or under low CO2 pressures, kerogen surface is weakly water-wet thanks to the hydrogen bonding between H2O and kerogen. As CO2 pressure increases, kerogen wettability shifts from water-wet to CO2-wet, because more CO2 molecules accumulate at the H2O-kerogen interface and a distinct CO2 thin film emerges. Density functional theory (DFT) calculations reveal that the O-containing functional groups preferably adsorb H2O molecules over CO2 through hydrogen bonding, which is responsible for the weakly water-wet tendency at low CO2 pressures. In contrast, the carbon skeleton of kerogen exhibits a stronger affinity to CO2, leading to the formation of CO2 thin film on the kerogen surface. The CO2 crowding close to the kerogen surface at high CO2 pressures gives rise to the CO2-wet state. This study provides, for the first time, the fundamental mechanism for the kerogen wettability transition from water-wet to CO2-wet. The work also indicates that wettability of the mature kerogen is more likely to be CO2-wet during GCS, which is unfavorable for capillary trapping of CO2, but is favorable for CO2-EOR.
Two tetrazole compounds (BTA, BTTA) self-assembled on copper substrate and their inhibition effect toward copper corrosion in 0.5 M H2SO4 was evaluated through atomic force microscopy (AFM), scanning ...electron microscopy (SEM), weight loss measurement along with electrochemical techniques including electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. Results indicate that BTTA can provide superior inhibition performance to BTA, and the highest inhibition efficiency values of 96.3% (BTA) and 99.8% (BTTA) were achieved respectively at 2 mM. Both tetrazole inhibitor films follow Langmuir model concerning both physical and chemical adsorption, which can be verified by X-ray photoelectronic spectroscopy (XPS) analysis. Besides, the negative value of adsorption free energy infers a spontaneous adsorption process of these tetrazole compounds on Cu surface. Molecular dynamics (MD) simulation reveals stronger multiple anchor adsorption of BTTA molecules than BTA because of the existence of S atom.
Direct laser writing is an efficient method for producing graphene on a substrate. This study investigated the formation of laser-induced graphene on silk fibers using molecular dynamics simulation ...and ReaxFF. The use of natural substrates such as silk fibers in laser-induced graphene has significant advantages in the industry due to their biodegradability and recyclability, making silk a preferred component in biomaterials and wearable biosensors. The study also looked into the diffusion coefficient of silk-derived laser-induced graphene using the MSD method and ReaxFF approach at varying temperatures and lengths. The simulation results showed that there is a non-linear relationship between the diffusion coefficient and temperature, while a linear relationship exists between the diffusion coefficient and graphene size. Interestingly, larger graphene structures exhibited a lower diffusion coefficient.
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PIM-1 kinase belongs to the Ser/Thr kinases family, an attractive therapeutic target for prostate cancer. Here, we screened about 100 natural substances to find potential PIM-1 inhibitors. Two ...natural compounds, Naringenin and Quercetin, were finally selected based on their PIM-1 inhibitory potential and binding affinities. The docking score of Naringenin and Quercetin with PIM-1 is −8.4 and − 8.1 kcal/mol, respectively. Fluorescence binding studies revealed a strong affinity (Ka values, 3.1 × 104 M−1 and 4.6 × 107 M−1 for Naringenin and Quercetin, respectively) with excellent IC50 values for Naringenin and Quercetin (28.6 μM and 34.9 μM, respectively). Both compounds inhibited the growth of prostate cancer cells (LNCaP) in a dose-dependent manner, with the IC50 value of Naringenin at 17.5 μM and Quercetin at 8.88 μM. To obtain deeper insights into the PIM-1 inhibitory effect of Naringenin and Quercetin, we performed extensive molecular dynamics simulation studies, which provided insights into the binding mechanisms of PIM-1 inhibitors. Finally, Naringenin and Quercetin were suggested to serve as potent PIM-1 inhibitors, offering targeted treatments of prostate cancer. In addition, our findings may help to design novel Naringenin and Quercetin derivatives that could be effective in therapeutic targeting of prostate cancer.
•PIM-1 is an attractive drug target for prostate cancer therapy.•We have discovered Naringenin and Quercetin as potent PIM-1 kinase inhibitors.•Docking and MD simulation studies suggested a strong binding and the formation of stable protein-ligands complexes.•Naringenin and Quercetin significantly inhibit the activity of PIM-1 with excellent IC50 values.•Both compounds show cytotoxic effect on LNCaP cells with admirable IC50 values.
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Graphene’s incredibly high thermal conductivity makes it a desirable material for heat dissipation and thermal management. A simple method of manufacturing graphene is the direct ...laser writing of rich carbon polymeric substrates, called laser-induced graphene (LIG); this is helpful in various applications, including sensors, catalysts, and supercapacitors. In this study, the thermal conductivity of cellulose and lignin-derived LIG (C-LIG and L-LIG) was investigated using the non-equilibrium molecular dynamics (NEMD) approach at various temperatures, lengths, and interatomic potentials, Airebo and opt-tersoff. This paper is the first study to investigate and calculate the thermal properties of laser-induced graphene, such as thermal conductivity coefficient and VDOS computations, using a molecular dynamics approach under various influential conditions (temperature, length, and interatomic potential). It particularly focuses on using biopolymers like lignin and cellulose to produce LIG. This study offers new and comprehensive insights into this type of graphene and the potential of these natural substrates for LIG production. The findings of this research were compared with those of defective and bi-layer graphene due to LIG’s bi-layer structure and various defects. The AIREBO potential leads to a much lower estimation of thermal conductivity than the Tersoff parameters themselves. This is due to neglecting out-of-plane scattering and the low velocities of transverse and longitudinal acoustic branches in the AIREBO potential. Finally, C-LIG has a higher thermal conductivity than L-LIG due to the fewer defects in C-LIG than L-LIG; however, using Opt-Tersoff potential led to a 20% decrease in thermal conductivity. The thermal conductivity coefficient of layered graphene falls as the number of layers rises due to long phonon paths, large grain size, and a regular structure. The VDOS result shows graphene’s prominent G-peak at approximately 50 THz.
•The BFE between root exudate components and LBDs of a PGPR strain were calculated.•Component with lowest BFE was the preferred chemoattractant for PGPR colonization.•The preferred chemoattractant ...was confirmed by capillary chemotaxis assay.•The preferred chemoattractant was confirmed by microcosm system.•ACC was the preferred chemoattractant for Pseudomonas sp. UW4 in the rhizosphere.
Unveiling the preferred chemoattractants of plant growth-promoting rhizobacteria (PGPR) toward the rhizosphere is crucial for engineering PGPR to improve their chemotactic rhizocompetence. Here, we selected 59 common components of root exudates and calculated the binding free energies between the components and the ligand-binding domains (LBDs) of 15 annotated chemoreceptors with extracellular LBDs in the genome of the PGPR strain Pseudomonas sp. UW4 using molecular docking and molecular dynamics (MD) simulation. The absolute values of the lowest binding free energies of 18 out of the 59 compounds with the LBDs and the logarithm of the UW4 capillary chemotaxis threshold concentrations for the 18 compounds showed a negative correlation. The binding free energy of 1-aminocyclopropane-1-carboxylate (ACC) with the LBD of the corresponding chemoreceptor WP116 was the lowest among the 59 root exudate components and the 15 chemoreceptor LBDs analyzed. Knocking out wp116 significantly reduced the chemotaxis rate of UW4 to the wheat rhizosphere in the microcosm system. These results showed that molecular docking and MD simulation are efficient for analyzing the affinities between the root exudates and the chemoreceptor extracellular LBDs of PGPR for identifying the preferred chemoattractant of PGPR toward the rhizosphere, and ACC was determined to be the preferred chemoattractant for Pseudomonas sp. UW4 in colonizing the rhizosphere.
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