Display omitted
•rGO-ZnO1-x nanosheet composites have been successfully in-situ synthesized.•rGO-ZnO1-x shows good response to ppb NO2 illuminated by white light at room temperature.•rGO-ZnO1-x ...exhibits much higher sensitivity, faster response and recovery than ZnO.•Molecular Dynamics and Langmuir adsorption model are used to build the sensing mechanism.
Recently, room-temperature gas sensors have become very attractive due to the fact that they can be operated without heating, and thus simplifying the sensor design, reducing the fabrication cost, decreasing the power consumption and increasing the long-term stability. In this study, we propose a facile one-step hydrothermal method to prepare a composite of reduced graphene (rGO)/oxygen-deficient zinc oxide (ZnO1-x), which exhibits obvious room-temperature gas sensing response. X-ray diffraction, Raman and X-ray photoelectron spectroscopy demonstrate that the rGO@ZnO1-x composite is successfully synthesized and large numbers of dual donor defects, oxygen vacancy and zinc interstitial, are introduced into the composite. Field-emission scanning electron microscopy and transmission electron microscopy results reveal that many nanoscale p-n junctions are in-situ formed between ZnO nanosheets and rGO sheets. UV–vis spectra show that the light absorption of the rGO@ZnO1-x composite is red-shifted and extended to the whole visible light region in comparison. The fraction of rGO in the composites plays an important role in the sensing performance. 2.0% is the optimal proportion to obtain the best sensing properties in terms of sensitivity, response and recovery times. The rGO@ZnO1-x composite exhibits significant responses to ppb-level NO2 with white LED light stimulation at room temperature. The enhanced sensing properties can be attributed to three factors: light activation, synergistic effects between rGO and ZnO1-x, and high concentration in donor defects. Molecular Dynamics (MD) is used to quantitively simulate the adsorption process, and the results show that the incorporation of rGO decreases the adsorption energy of NO2. It means that more NO2 species would adsorb on the rGO@ZnO1-x composites, which greatly improves the sensitivity. A new gas sensing mechanism based on the MD calculated results and Langmuir adsorption model is used to explain the reason that the rGO@ZnO1-x composites have a much faster response and recovery process. In addition, the rGO@ZnO1-x sensor shows a weaker response to other interference gases.
Recently, the world has witnessed outbreak of a novel Coronavirus (SARS-CoV-2), the virus which initially emerged in Wuhan, China has now made its way to a large part of the world, resulting in a ...public emergency of international concern. The functional importance of Chymotrypsin-like protease (3CL
pro
) in viral replication and maturation turns it into an attractive target for the development of effective antiviral drugs against SARS and other coronaviruses. At present, there is no standard drug regime nor any vaccine available against the infection. The rapid development and identification of efficient interventions against SARS-CoV-2 remains a major challenge. Based on the available knowledge of closely related coronavirus and their safety profiles, repurposing of existing antiviral drugs and screening of available databases is considered a near term strategic and economic way to contain the SARS-CoV-2 pandemic. Herein, we applied computational drug design methods to identify Chymotrypsin-like protease inhibitors from FDA approved antiviral drugs and our in-house database of natural and drug-like compounds of synthetic origin. As a result three FDA approved drugs (Remdesivir, Saquinavir and Darunavir) and two natural compounds (. flavone and coumarine derivatives) were identified as promising hits. Further, MD simulation and binding free energy calculations were performed to evaluate the dynamic behavior, stability of protein-ligand contact, and binding affinity of the hit compounds. Our results indicate that the identified compounds can inhibit the function of Chymotrypsin-like protease (3CL
pro
) of Coronavirus. Considering the severity of the spread of coronavirus, the current study is in-line with the concept of finding the new inhibitors against the vital pathway of the corona virus to expedite the process of drug discovery.
Communicated by Ramaswamy H. Sarma
SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the ...scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (M
pro
) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of −87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against M
pro
of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.
Communicated by Ramaswamy H. Sarma
Ykt6 is one of the most conserved SNARE (N-ethylmaleimide-sensitive factor attachment protein receptor) proteins involved in multiple intracellular membrane trafficking processes. The ...membrane-anchoring function of Ykt6 has been elucidated to result from its conformational transition from a closed state to an open state. Two ways of regulating the conformational transition were proposed: the C-terminal lipidation and the phosphorylation at the SNARE core. Despite many aspects of common properties, Ykt6 displays differential cellular localizations and functional behaviors in different species, such as yeast, mammals, and worms. The structure–function relationship underlying these differences remains elusive. Here, we combined biochemical characterization, single-molecule FRET measurement, and molecular dynamics simulation to compare the conformational dynamics of yeast and rat Ykt6. Compared to rat Ykt6 (rYkt6), yeast Ykt6 (yYkt6) has more open conformations and could not bind dodecylphosphocholine that inhibits rYkt6 in the closed state. A point mutation T46L/Q57A was shown to be able to convert yYkt6 to a more closed and dodecylphosphocholine-bound state, where Leu46 contributes key hydrophobic interactions for the closed state. We also demonstrated that the phospho-mutation S174D could shift the conformation of rYkt6 to a more open state, but the corresponding mutation S176D in yYkt6 leads to a slightly more closed conformation. These observations shed light on the regulatory mechanism underlying the variations of Ykt6 functions across species.
We performed molecular dynamics (MD) simulations for the responses of single crystal (SC) and nanotwinned (nt) diamond films under nanoindentation, respectively, aimed to uncover the effects of twin ...boundary (TB) and twin thickness (δ) on hardness (H) and the corresponding deformation mechanisms. We found the Hall-Petch type relationship between H and δ. We also found that the inelastic deformation of SC-diamond under indentation could mainly be attributed to the nucleation and propagation of 〈110〉{111} dislocation loops. It showed that dislocation blockage and pile up at the TBs may induce additional hardening of the nt-diamond, while the softening of the material could be attributed to: (i) the formation and movement of the dislocation loops parallel with the surface, and (ii) the breakage of TBs, which may serve as new sites for dislocations nucleation.
•19 compounds from Neem extract tested against 7 standard anti-COVID drugs for action on PLpro of latter.•All 19 NEEM molecules show better docking, ADME results vis-a-vis standard drugs.•Among the ...19, desacetylgedunin (DCG) gives highest docking score with PLpro.•MD simulation of shows binding with DCG induces large structural change on PLpro.
Azadirachta Indica (Neem) extracts have been known for their anti-bacterial and other effects since ancient times. The present work examines the inhibitory activity of Neem extracts on Papain like protease (PLpro) of the novel coronavirus SARS-CoV-2. The activity is analysed by molecular docking study along with molecular dynamics simulation. All the studied Neem compounds showed decent level of inhibitory activity against PLpro of SARS-CoV-2. Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro. Furthermore, MD-simulation studies supported by standard analysis (e.g. root mean square deviation and fluctuation (RMSD, RMSF), radius of gyration, solvent accessible surface area (SASA)) showed large impact on the structure of PLpro by DCG. We believe that the significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2.
Display omitted
Let-7 was one of the first microRNAs (miRNAs) to be discovered and its expression promotes differentiation during development and function as tumor suppressors in various cancers. The maturation ...process of let-7 miRNA is tightly regulated by multiple RNA-binding proteins. For example, LIN28 binds to the terminal loops of the precursors of let-7 family and block their processing into mature miRNAs. Trim25 promotes the uridylation-mediated degradation of pre-let-7 modified by LIN28/TUT4. Recently, human pseudouridine synthase TruB1 has been reported to facilitate let-7 maturation by directly binding to pri-let-7 and recruiting Drosha-DGCR8 microprocessor. Through biochemical assay and structural investigation, we show that human TruB1 binds specifically the terminal loop of pri-let-7a1 at nucleotides 31–41, which folds as a small stem-loop architecture. Although TruB1 recognizes the terminal loop of pri-let-7a1 in a way similar to how E. coli TruB interacts with tRNA, a conserved KRKK motif in human and other higher eukaryotes adds an extra binding interface and strengthens the recognition of TruB1 for pri-let-7a1 through electrostatic interactions. These findings reveal the structural basis of TruB1-pri-let-7 interaction which may assists the elucidation of precise role of TruB1 in biogenesis of let-7.
•Human pseudouridine synthase TruB1 binds specifically the terminal loop of pri-let-7a1 at nucleotides 31–41 to facilitate let-7 maturation.•Apo-form crystal structure and RNA-bound model of TruB1 reveal the interaction mode between TruB1 and pri-let-7a1.•TruB1 in human and other higher eukaryotes evolve to have an KRKK motif to strengthen its recognition for pri-let-7a1.
•MOF-74(Ni)@GrO composites synthesized via hydrothermal route.•Synthesized composites were characterized using several analytical techniques.•The MD simulation was applied using the LAMMPS ...package.•The CO2 adsorption performance of MOF-74(Ni)@GrO composites was estimated numerically and experimentally through MD simulation.•The CO2/N2 selectivity was evaluated experimentally and numerically.•The CO2 uptake capacity of the composite showed a 52% improvement in both studies.
Given the significant impact of carbon dioxide emissions on current and future human life, the imperative for CO2 reduction becomes evident. Metal-organic frameworks (MOFs) composites stand out as highly effective adsorbents for CO2 capture and separation. In this study, MOF-74(Ni)@graphene oxide (GrO) composites were successfully generated through a hydrothermal synthesis route. The thermal, pore, and textural properties of the new MOF composites were experimentally tested through TGA, N2 adsorption–desorption, XRD, and FTIR. The adsorption and separation characteristics of the new MOF composites were evaluated through experimental and molecular dynamic (MD) simulation studies at ambient conditions. Interestingly, the BET surface area of all composites significantly increased compared to the pristine MOF. Among all composites, MOF-74(Ni)@GrO-10 demonstrated the highest value, surpassing others by 1060 cm2/g. MOF-74(Ni)@GrO-10 composite demonstrates the maximum amount of CO2 uptake capacity of 5.76 mmol/g experimentally and 6.65 mmol/g numerically, evidencing a substantial enhancement of 25 % and 28 % in comparison to the pristine MOF-74(Ni). The determination of CO2/N2 selectivity for all samples was carried out through a single-component isotherm under post-combustion conditions (PCO2/PN2: 0.15 bar/ 0.75 bar). Concerning CO2/N2 selectivity, the MOF-74(Ni)@GrO-10 composite also displayed the highest selective adsorption values of 44 and 45 experimentally and numerically, respectively. This marks a significant 7 % enhancement compared with the bare MOF. MOF-74(Ni)@GrO-10 exhibited a significantly higher heat of CO2 adsorption compared to bare MOF-74.As evidenced by both experimental and numerical results, MOF-74(Ni)@GrO-10 indicated 37 kJ/mol and 39 kJ/mol, and MOF-74(Ni) showed 34.5 kJ/mol and 36.5 kJ/mol heat of CO2 adsorption, implying that CO2 molecules have a stronger interaction with the composite adsorbent than the bare MOF. MOF-74(Ni)@GrO-10 also exhibited high stability, preserving 95 % of its structure after five consecutive adsorption–desorption cycles in both studies. The research finding implies that MOF-74(Ni)@GrO-10 is a promising adsorbent that can be widely used in adsorption and separation technology.
In this study, we investigated the deliquescence of NaBH4 thin films under atmospheric conditions toward their hydrogen supply application. Upon exposed to air, the film deliquesced along with ...generating hydrogen due to the decomposition of BH4- ions, but the decomposition rate was slow enough for a sizable amount of BH4- ions remained stable in the deliquesced film. As a result, a reversible deliquescence-recrystallization cycle in the NaBH4 thin film could be achieved through control of humidity. Molecular dynamics simulations suggested that Na+ and BH4- ions tended to neighbor each other with almost the same intra-distance as that in the crystal. A kind of such local ordered structures in deliquesced NaBH4 may prevent an excess hydration and subsequent decomposition of BH4- ions and is responsible for the stability of BH4- ions, enabling the reversible deliquescence-recrystallization cycle. These combined experimental and theoretical insights offer new perspectives on controlling hydrogen release from borohydrides based on humidity conditions in the thin film form.
•Deliquescence of NaBH4 thin films on Si (100) substrates explored.•Raman spectra confirm prevalence of BH4- ions in deliquesced state.•In-situ XRD reveals reversible recrystallization and deliquescence cycle.•MD simulations suggest local molecular-like structure prevents excess hydration.•Insights gained into controlled hydrogen release, offering novel borohydride applications.
Molecular modeling in drug discovery Adelusi, Temitope Isaac; Oyedele, Abdul-Quddus Kehinde; Boyenle, Ibrahim Damilare ...
Informatics in medicine unlocked,
2022, Letnik:
29
Journal Article
Recenzirano
Odprti dostop
With the financial requirements and high time associated with bringing a commercial drug to the market, the application of computer-aided drug design has been recognized as a powerful technology in ...the drug discovery pipeline. In accelerating drug discovery, molecular modeling techniques have experienced considerable growth in computational capabilities over the last decade. Pharmaceutical companies and academic research organizations are currently using various computational modeling techniques to lower the cost and time required for the discovery of an effective drug. In this article, we focus on reviewing three key components of molecular modeling (Molecular Docking, Molecular Dynamics, and ADMET modeling), their applications, and limitations in small-molecule drug discovery. We discussed the technicalities encircling molecular dynamics and docking, the algorithms used to develop the docking softwares, and the models explored by these algorithms coupled with their scoring functions. We also reviewed the influence of molecular dynamics simulations (all atoms and coarse-grained molecular dynamics simulations) in drug discovery and also elucidated how the ensembles generated from MD simulations could pave the way for novel drug discovery. Furthermore, we briefly explain the role played by pharmacokinetics and pharmacodynamics profiling in discovering new leads for therapeutic efficacy. Besides the computational success of molecular modeling in drug discovery, we highlighted the experimental corroboration of in silico discovered drug candidates. However, as there is hardly a drug in the market discovered primarily with the use of computational modeling, we concluded the review by proposing possible solutions that could foster the advancement and clinical success of drugs.
PDF
![Stable nature of [BH4]− ion...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0360-3199/small "Stable nature of [BH4]− ions in deliquescence thin-film NaBH4 and humidity control of their decomposition toward hydrogen supply and storage application")
