An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent tr...An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent transition metal diboride powders.The(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardness of 31.2±2.1 GPa and resisted 36.9 GPa of stress before delamination,as observed at the interface.The temperature-dependent thermal properties of the multicomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by molecular dynamics(MD)simulations driven by a machine learning force field(MLFF)trained on density functional theory(DFT)calculations.The thermal conductivity,density,heat capacity,and coefficient of thermal expansion obtained by the MD simulations were used in time-dependent thermal stress finite element model(FEM)simulations.The low thermal conductivity(<6.52 W·m^(-1)·K^(-1))of the multicomponent diboride coupled with its similar coefficient of thermal expansion to that of graphite indicated that stresses of less than 10 GPa were generated at the interface at high temperatures,and therefore,the coating was mechanically resistant to the thermal stress induced during ablation.Ablation experiments at 220℃ showed that the multicomponent diboride coating was resistant to thermal stresses with no visible cracking or delamination.The ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides,which caused a decrease in the mass and thickness of the coating and resulted in mass and linear ablation rates of-0.51 mg·s^(-1) and -1.38μm·s^(-1),respectively,after 60 s.These findings demonstrated the thermal and mechanical stability of multicomponent entropy-stabilized diborides as coatings for carbon materials in engineering components under extreme environments.展开更多
Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new thera...Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.展开更多
Molecular dynamics （MD） simulations are performed to investigate the wettability of liquid metal on the metal sub- strate. Results show that there exists different wettability on the different metal substrates, whic...Molecular dynamics （MD） simulations are performed to investigate the wettability of liquid metal on the metal sub- strate. Results show that there exists different wettability on the different metal substrates, which is mainly determined by the interaction between the liquid and the substrate. The liquid metal is more likely to wet the same kind of metal substrate, which attracts the liquid metal to one side on the hybrid substrate. Exchanging the liquid metal and substrate metal has no effect on the wettability between these two metals. Moreover, the study of metal drop coalescing indicates that the metal substrate can significantly affect the coalescence behavior, in which the changeable wettability of liquid metal plays a predominant role. These studies demonstrate that the wetting behavior of liquid metal can be controlled by choosing the suitable metal substrate.展开更多
Control of ion transport and fluid flow through nanofluidic devices is of primary importance for energy storage and conversion, drug delivery and a wide range of biological processes. Recent development of nanotechnol...Control of ion transport and fluid flow through nanofluidic devices is of primary importance for energy storage and conversion, drug delivery and a wide range of biological processes. Recent development of nanotechnology, synthesis techniques, purification technologies, and experiment have led to rapid advances in simulation and modeling studies on ion transport properties. In this review, the applications of Poisson-Nernst-Plank （PNP） equations in analyzing transport properties are presented. The molecular dynamics （MD） studies of transport properties of ion and fluidic flow through nanofluidic devices are reported as well.展开更多
HDAC8 is an important target for the treatment of many cancers and other diseases. To develop potent and selective HDAC8 inhibitors, molecular docking and molecular dynamics(MD) simulations were employed for investiga...HDAC8 is an important target for the treatment of many cancers and other diseases. To develop potent and selective HDAC8 inhibitors, molecular docking and molecular dynamics(MD) simulations were employed for investigation of the mechanism of HDAC8 inhibitions containing hydroxamic acid group. Compound 1 with high activity and compound 2 with low activity were selected for comparative study. Compound 1 formed a stronger chelation with Zn ion and was more stable in the HDAC8 pocket than compound 2. Residues HIS-180, ASP-178, ASP-267, and GLY-140 played a critical role in securing the position of compound 1. Both the head and tail of compound 1 formed strong hydrogen bonds with ASP-178, facilitating the ZBG of compound 1 close to the Zn ion so that they formed permanent chelation during the simulation period. The Cap group of the compounds with branch and long chains was advantageous to form interaction with active pocket opening. What’s more, based on the results of this study, three innovative recommendations for the design of highly active HDAC8 inhibitors were presented, which will be useful for the development of new HDAC8 inhibitors.展开更多
The further interaction mechanism towards renin inhibitors was revealed by comparison of renin with different active inhibitors in aqueous solution.Molecular docking and molecular dynamics(MD)simulations were combined...The further interaction mechanism towards renin inhibitors was revealed by comparison of renin with different active inhibitors in aqueous solution.Molecular docking and molecular dynamics(MD)simulations were combined for the research.The results reflected that electrostatic and hydrophobic effects were the major interactions for renin inhibitors forming complexes with renin,and some residues were the key to the formation of complex,especially Asp38/Asp226.The factor of different activities performed in renin inhibitors was illustrated as well.For the higher active renin inhibitor,it possessed stronger affinity with renin,and its detected conformation was more extended to fit for the key binding site.This promoted the capacity to form special interactions with the key residues.While conformation of the lower active renin inhibitor performed folded in the active site of renin,the interactions to the important pocket S3sp was restricted,resulting in undesirable bioactivity.展开更多
Superhydrophobic(SH)coatings are intended to resist a surface from corrosion and thereby increases the product life duration.It is also a promising solution to save cleaning costs and time by providing self-clea...Superhydrophobic(SH)coatings are intended to resist a surface from corrosion and thereby increases the product life duration.It is also a promising solution to save cleaning costs and time by providing self-clean nature to the surface.This review article provides the most recent updates in designing SH surfaces and their characterizations adopted both in experimental and computational techniques.To gain a comprehensive perspective,the SH surfaces present in nature those are inspiring human beings to mimic such surfaces are introduced at the beginning of this article.Subsequently,different fabrication techniques undertaken recently to design artificial SH surfaces are briefly discussed.Recent progress in computations employed in the development of SH surfaces is then discussed.Next,the limitations in SH surfaces are addressed.Finally,perceptiveness of different strategies and their limitations are presented in the concluding remarks and outlook.Overall,this mini review article brings together and highlights the significant advancements in fabrication of superhydrophobic surfaces which may surely help the early-stage researchers/scientists to plan their work accordingly.展开更多
All-atom molecular dynamics （MD） simulations and chemical shifts were used to study interactions and structures in the glycine-water system. Radial distribution functions and the hydrogen-bond network were applied i...All-atom molecular dynamics （MD） simulations and chemical shifts were used to study interactions and structures in the glycine-water system. Radial distribution functions and the hydrogen-bond network were applied in MD simulations. Aggregates in the aqueous glycine solution could be classified into different regions by analysis of the hydrogen-bonding network. Temperature-dependent NMR spectra and the viscosity of glycine in aqueous solutions were measured to compare with the results of MD simulations. The variation tendencies of the hydrogen atom chemical shifts and viscosity with concentration of glycine agree with the statistical results of hydrogen bonds in the MD simulations.展开更多
基金This work was supported by the Swedish Foundation for Strategic Research(SSF)for Infrastructure Fellowship(No.RIF14-0083)The authors thank Lars Frisk for the ablation setup and testing and for the coefficient of thermal expansion measurements.The authors also acknowledge the Lulea Material Imaging and Analysis(LUMIA)Center for providinggthe imaging characterization equipment.Daniel’Hedman acknowledges financial support from the Institute for Basic Science,Republic of Korea(No.IBS-RO19-DI)+1 种基金The authors would like to acknowledge the computational resources provided by the National Academic Infrastructure for Supercomputing in Sweden(NAISS)via the NAISS 2023/3-31 and NAISS 2023/6-292 projects,which were partially funded by the Swedish Research Council(No.2022-06725)In addition,computational resources were provided by the Institute for Basic Science(Republic of Korea)at the HPC clusters Cimulator(CMCM,Ulsan)and Olaf(IBS-HQ,Daejeon).
文摘An entropy-stabilized multicomponent ultrahigh-temperature ceramic(UHTC)coating,(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2),on a graphite substrate was in-situ sintered by spark plasma sintering(SPs)from constituent transition metal diboride powders.The(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) coating had a hardness of 31.2±2.1 GPa and resisted 36.9 GPa of stress before delamination,as observed at the interface.The temperature-dependent thermal properties of the multicomponent diboride(Ti_(0.25)V_(0.25)Zr_(0.25)Hf_(0.25))B_(2) were obtained by molecular dynamics(MD)simulations driven by a machine learning force field(MLFF)trained on density functional theory(DFT)calculations.The thermal conductivity,density,heat capacity,and coefficient of thermal expansion obtained by the MD simulations were used in time-dependent thermal stress finite element model(FEM)simulations.The low thermal conductivity(<6.52 W·m^(-1)·K^(-1))of the multicomponent diboride coupled with its similar coefficient of thermal expansion to that of graphite indicated that stresses of less than 10 GPa were generated at the interface at high temperatures,and therefore,the coating was mechanically resistant to the thermal stress induced during ablation.Ablation experiments at 220℃ showed that the multicomponent diboride coating was resistant to thermal stresses with no visible cracking or delamination.The ablation mechanisms were mechanical denudation and evaporation of B_(2)O_(5) and light V-Ti oxides,which caused a decrease in the mass and thickness of the coating and resulted in mass and linear ablation rates of-0.51 mg·s^(-1) and -1.38μm·s^(-1),respectively,after 60 s.These findings demonstrated the thermal and mechanical stability of multicomponent entropy-stabilized diborides as coatings for carbon materials in engineering components under extreme environments.
文摘Human sodium-glucose cotransporter 2 (hSGLT2) is a membrane protein responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule. Inhibition of hSGLT2 has been regarded as a brand new therapeutic approach for the treatment of type 2 diabetes mellitus (T2DM) due to its non-insulin related characteristics with less side effects. Current commercially available hSGLT2 inhibitors are all C-glycoside inhibitors. Previous studies have reported that N-glycoside inhibitors have better potential to serve as new drugs due to their good metabolic stability. In addition, non-glycoside inhibitors have been shown to exhibit the capability to overcome the existing problems of current glycoside inhibitors, including low tissue permeability, poor stability and short serum half-time. Here, we aimed to discover novel N-glycoside and non-glycoside hSGLT2 inhibitors by a combination of several computational approaches. A ligand-based pharmacophore model was generated, well validated and subsequently utilized as a 3D query to identify novel hSGLT2 inhibitors from National Cancer Institute (NCI) and Traditional Chinese Medicine (TCM) databases. Finally, one N-glycoside (NSC679207) and one non-glycoside (TCM_Piperenol_A) hSGLT2 inhibitors were successfully identified, which were proven to exhibit excellent binding affinities, pharmacokinetic properties and less toxicity than the commercially available hSGLT2 inhibitor, canagliflozin, via molecular docking, ADMET prediction, molecular dynamics (MD) simulations and binding free energy calculations. All together, our results strongly suggest that these two compounds have great potential to serve as novel hSGLT2 inhibitors for the treatment of T2DM and their efficacies may be further examined by a series of in vitro and/or in vivo bioassays.
基金supported by the National Natural Science Foundation of China(Grant No.51671114)the Special Funding in the Project of the Taishan Scholar Construction Engineeringthe National Key Research Program of China(Grant No.2016YFB0300501)
文摘Molecular dynamics （MD） simulations are performed to investigate the wettability of liquid metal on the metal sub- strate. Results show that there exists different wettability on the different metal substrates, which is mainly determined by the interaction between the liquid and the substrate. The liquid metal is more likely to wet the same kind of metal substrate, which attracts the liquid metal to one side on the hybrid substrate. Exchanging the liquid metal and substrate metal has no effect on the wettability between these two metals. Moreover, the study of metal drop coalescing indicates that the metal substrate can significantly affect the coalescence behavior, in which the changeable wettability of liquid metal plays a predominant role. These studies demonstrate that the wetting behavior of liquid metal can be controlled by choosing the suitable metal substrate.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11374243 and 11574256)
文摘Control of ion transport and fluid flow through nanofluidic devices is of primary importance for energy storage and conversion, drug delivery and a wide range of biological processes. Recent development of nanotechnology, synthesis techniques, purification technologies, and experiment have led to rapid advances in simulation and modeling studies on ion transport properties. In this review, the applications of Poisson-Nernst-Plank （PNP） equations in analyzing transport properties are presented. The molecular dynamics （MD） studies of transport properties of ion and fluidic flow through nanofluidic devices are reported as well.
基金Talents Introduction Foundation for Universities of Guangdong Province(GD 2011)the Science and Technology Planning Project of Guangzhou(No.2013J4100071)。
文摘HDAC8 is an important target for the treatment of many cancers and other diseases. To develop potent and selective HDAC8 inhibitors, molecular docking and molecular dynamics(MD) simulations were employed for investigation of the mechanism of HDAC8 inhibitions containing hydroxamic acid group. Compound 1 with high activity and compound 2 with low activity were selected for comparative study. Compound 1 formed a stronger chelation with Zn ion and was more stable in the HDAC8 pocket than compound 2. Residues HIS-180, ASP-178, ASP-267, and GLY-140 played a critical role in securing the position of compound 1. Both the head and tail of compound 1 formed strong hydrogen bonds with ASP-178, facilitating the ZBG of compound 1 close to the Zn ion so that they formed permanent chelation during the simulation period. The Cap group of the compounds with branch and long chains was advantageous to form interaction with active pocket opening. What’s more, based on the results of this study, three innovative recommendations for the design of highly active HDAC8 inhibitors were presented, which will be useful for the development of new HDAC8 inhibitors.
基金supported by Talents Introduction Foundation for Universities of Guangdong Province (GD 2011)the Science and Technology Planning Project of Guangzhou (No. 2013J4100071)
文摘The further interaction mechanism towards renin inhibitors was revealed by comparison of renin with different active inhibitors in aqueous solution.Molecular docking and molecular dynamics(MD)simulations were combined for the research.The results reflected that electrostatic and hydrophobic effects were the major interactions for renin inhibitors forming complexes with renin,and some residues were the key to the formation of complex,especially Asp38/Asp226.The factor of different activities performed in renin inhibitors was illustrated as well.For the higher active renin inhibitor,it possessed stronger affinity with renin,and its detected conformation was more extended to fit for the key binding site.This promoted the capacity to form special interactions with the key residues.While conformation of the lower active renin inhibitor performed folded in the active site of renin,the interactions to the important pocket S3sp was restricted,resulting in undesirable bioactivity.
基金support from the National Natural Science Foundation of China (Grant No. 51271100)the National Basic Research Program of China (Grant No.2012CB825702)supported by the Special Funding in the Project of the Taishan Scholar Construction Engineering
文摘Superhydrophobic(SH)coatings are intended to resist a surface from corrosion and thereby increases the product life duration.It is also a promising solution to save cleaning costs and time by providing self-clean nature to the surface.This review article provides the most recent updates in designing SH surfaces and their characterizations adopted both in experimental and computational techniques.To gain a comprehensive perspective,the SH surfaces present in nature those are inspiring human beings to mimic such surfaces are introduced at the beginning of this article.Subsequently,different fabrication techniques undertaken recently to design artificial SH surfaces are briefly discussed.Recent progress in computations employed in the development of SH surfaces is then discussed.Next,the limitations in SH surfaces are addressed.Finally,perceptiveness of different strategies and their limitations are presented in the concluding remarks and outlook.Overall,this mini review article brings together and highlights the significant advancements in fabrication of superhydrophobic surfaces which may surely help the early-stage researchers/scientists to plan their work accordingly.
基金Supported by the National Natural Science Foundation of China(No.20903026)the Talents Introduction Foundation for Universities of Guangdong Province(2011)Scientific Research Foundation of the Natural Science Foundation of Guangdong Province(No.S2011010002483)
文摘All-atom molecular dynamics （MD） simulations and chemical shifts were used to study interactions and structures in the glycine-water system. Radial distribution functions and the hydrogen-bond network were applied in MD simulations. Aggregates in the aqueous glycine solution could be classified into different regions by analysis of the hydrogen-bonding network. Temperature-dependent NMR spectra and the viscosity of glycine in aqueous solutions were measured to compare with the results of MD simulations. The variation tendencies of the hydrogen atom chemical shifts and viscosity with concentration of glycine agree with the statistical results of hydrogen bonds in the MD simulations.
