Abundant evidences of higher sea levels from Jiangsu and Fujian coasts have proved a marine transgression event during 30–40 ka BP, suggesting that there was a stage with high sea level and a warm climate when ice sh...Abundant evidences of higher sea levels from Jiangsu and Fujian coasts have proved a marine transgression event during 30–40 ka BP, suggesting that there was a stage with high sea level and a warm climate when ice sheets shrank in the Northern Hemisphere. The duration of 30–40 ka BP spanned a period in the late Marine Isotope Stage 3（MIS 3） and was in nature an interstadial epoch during the Last Glacial period of the Quaternary. Different from the glacial period with a cold climate, this marine transgression considered as a penultimate higher sea level during the Quaternary remains a puzzle that why the evidence is contrary to the Quaternary glacial theory. It is important to understand sea level rise for these areas sensitively responding to the global changes in the future. To recognize the key issues on sea level changes, the eustatic sea level（H_S） was defined as the glaciation-climateforced sea levels, and the relative sea level change（H_R） was defined as that a sea level record was preserved in sediment that experienced multiple secondary actions of land and sea effects. On the basis as defined above, we constructed multi-level models of climate-driven glacio-eustatic changes and land-sea systems. By integrating data sets from eight borehole cores and prescribing the boundary conditions, we simulated the changes of HS and HR in the East China Sea and southern Yellow Sea areas in the late MIS 3. The marine transgression strata from the borehole core data was identified at ca. 30 m below present sea level as a result of the collective influence of ice melting water, neotectonic subsidence, sediment compaction and terrestrial sediment filling since ca. 35 ka ago,whereas the simulated relative sea-levels turned out to be –26.3––29.9 m a.s.l. The small error involved in the simulation results of ±（2.5–4.5） m demonstrated the credibility of the results. Our results indicated that sea level change in the late MIS 3 was dominated by glacial effects, in which the eustatic sea-level was between –19.2––22.1m a.s.l. The study sheds light on the nature of sea-level changes along the east coast of China in the late MIS 3 and contributes to understanding the characteristics of marine transgression under the effects of multiple complex land-sea interactions.展开更多
Structural elasticity of double-strand DNAs is very important for their biological functions such as DNA-ligand binding and DNA-protein recognition.By all-atom molecular dynamics simulations,we investigated the bendin...Structural elasticity of double-strand DNAs is very important for their biological functions such as DNA-ligand binding and DNA-protein recognition.By all-atom molecular dynamics simulations,we investigated the bending elasticity of DNA with three typical sequences including poly(A)-poly(T)(AA-TT),poly(AT)-poly(TA)(AT-TA),and a generic sequence(GENE).Our calculations indicate that,AA-TT has an apparently larger bending persistence length(P~63 nm)than GENE(P~49 nm)and AT-TA(P~48 nm)while the persistence length of AT-TA is only very slightly smaller than that of GENE,which agrees well with those from existing works.Moreover,through extensive electrostatic calculations,we found that the sequence-dependent bending elasticity is attributed to the sequence-dependent electrostatic bending energy for AA-TT,AT-TA and GENE,which is coupled to their backbone structures.Particularly,the apparently stronger bending stiffness of AA-TT is attributed to its narrower minor groove.Interestingly,for the three DNAs,we predicted the non-electrostatic persistence length of~17 nm,thus electrostatic interaction makes the major contribution to DNA bending elasticity.The mechanism of electrostatic energy dominating sequence effect in DNA bending elasticity is furtherly illustrated through the electrostatic calculations for a grooved coarse-grained DNA model where minor groove width and other microscopic structural parameters can be artificially adjusted.展开更多
The lubrication characteristics of liquid crystal(LC) molecules sheared between two crystalline surfaces obtained from molecular dynamics(MD) simulations are reported in this article.We consider a coarse-grained rigid...The lubrication characteristics of liquid crystal(LC) molecules sheared between two crystalline surfaces obtained from molecular dynamics(MD) simulations are reported in this article.We consider a coarse-grained rigid bead-necklace model of the LC molecules confined between two atomic surfaces subject to different shearing velocities.A systematic study shows that the slip length of LC lubrication changes significantly as a function of the LC-surface interaction energy,which can be well described though a theoretical curve.The slip length increases as shear rate increases at high LC-surface interaction energy.However,this trend can not be observed for low interaction energy.The orientation of the LC molecules near the surface is found to be guided by the atomics surfaces.The influence of temperature on the lubrication characteristics is also discussed in this article.展开更多
Protein-protein interactions are vital for a wide range of biological processes.The interactions between the hypoxia-inducible factor and von Hippel Lindau(VHL)are attractive drug targets for ischemic heart disease.In...Protein-protein interactions are vital for a wide range of biological processes.The interactions between the hypoxia-inducible factor and von Hippel Lindau(VHL)are attractive drug targets for ischemic heart disease.In order to disrupt this interaction,the strategy to target VHL binding site using a hydroxyproline-like(pro-like)small molecule has been reported.In this study,we focused on the inhibition mechanism between the pro-like inhibitors and the VHL protein,which were investigated via molecular dynamics simulations and binding free energy calculations.It was found that pro-like inhibitors showed a strong binding affinity toward VHL.Binding free energy calculations and free energy decompositions suggested that the modification of various regions of pro-like inhibitors may provide useful information for future drug design.展开更多
Recent advancements in nanotechnology have spotlighted the catalytic potential of nanozymes, particularly single-atom nanozymes(SANs), which are pivotal for innovations in biosensing and medical diagnostics. Among oth...Recent advancements in nanotechnology have spotlighted the catalytic potential of nanozymes, particularly single-atom nanozymes(SANs), which are pivotal for innovations in biosensing and medical diagnostics. Among others, DNA stands out as an ideal biological regulator. Its inherent programmability and interaction capabilities allow it to significantly modulate nanozyme activity. This study delves into the dynamic interplay between DNA and molybdenum-zinc single-atom nanozymes(Mo-Zn SANs). Using molecular dynamics simulations, we uncover how DNA influences the peroxidase-like activities of Mo-Zn SANs, providing a foundational understanding that broadens the application scope of SANs in biosensing.With these insights as a foundation, we developed and demonstrated a model aptasensor for point-ofcare testing(POCT), utilizing a label-free colorimetric approach that leverages DNA-nanozyme interactions to achieve high-sensitivity detection of lysozyme. Our work elucidates the nuanced control DNA exerts over nanozyme functionality and illustrates the application of this molecular mechanism through a smartphone-assisted biosensing platform. This study not only underscores the practical implications of DNA-regulated Mo-Zn SANs in enhancing biosensing platforms, but also highlights the potential of single-atom nanozyme technology to revolutionize diagnostic tools through its inherent versatility and sensitivity.展开更多
Eutectic high entropy alloys are noted for their excellent castability and comprehensive mechanical properties.The excellent mechanical properties are closely related to the activation and evolution of deformation mec...Eutectic high entropy alloys are noted for their excellent castability and comprehensive mechanical properties.The excellent mechanical properties are closely related to the activation and evolution of deformation mechanisms at the atomic scale.In this work,AlCoCrFeNi2.1 alloy is taken as the research object.The mechanical behaviors and deformation mechanisms of the FCC and B2 single crystals with different orientations and the FCC/B2 composites with K-S orientation relationship during nanoindentation processes are systematically studied by molecular dynamics simulations.The results show that the mechanical behaviors of FCC single crystals are significantly orientation-dependent,meanwhile,the indentation force of[110]single crystal is the lowest at the elastic-plastic transition point,and that for[100]single crystal is the lowest in plastic deformation stage.Compared with FCC,the stress for B2 single crystals at the elastic-plastic transition point is higher.However,more deformation systems such as stacking faults,twins and dislocation loops are activated in FCC single crystal during the plastic deformation process,resulting in higher indentation force.For composites,the flow stress increases with the increase of B2 phase thickness during the initial stage of deformation.When indenter penetrates heterogeneous interface,the significantly increased deformation system in FCC phase leads to a significant increase in indentation force.The mechanical behaviors and deformation mechanisms depend on the component single crystal.When the thickness of the component layer is less than 15 nm,the heterogeneous interfaces fail to prevent the dislocation slip and improve the indentation force.The results will enrich the plastic deformation mechanisms of multi-principal eutectic alloys and provide guidance for the design of nanocrystalline metallic materials.展开更多
Uranium–molybdenum(U–Mo) alloys are critical for nuclear power generation and propulsion because of their superior thermal conductivity, irradiation stability, and anti-swelling properties. This study explores the p...Uranium–molybdenum(U–Mo) alloys are critical for nuclear power generation and propulsion because of their superior thermal conductivity, irradiation stability, and anti-swelling properties. This study explores the plastic deformation mechanisms of γ-phase U–Mo alloys using molecular dynamics(MD) simulations. In the slip model, the generalized stacking fault energy(GSFE) and the modified Peierls–Nabarro(P–N) model are used to determine the competitive relationships among different slip systems. In the twinning model, the generalized plane fault energy(GPFE) is assessed to evaluate the competition between slip and twinning. The findings reveal that among the three slip systems, the {110}<111>slip system is preferentially activated, while in the {112}<111> system, twinning is favored over slip, as confirmed by MD tensile simulations conducted in various directions. Additionally, the impact of Mo content on deformation behavior is emphasized. Insights are provided for optimizing process conditions to avoid γ → α′′ transitions, thereby maintaining a higher proportion of γ-phase U–Mo alloys for practical applications.展开更多
The experiment explored the Fe_(2)O_(3) reduction process with H_(2)/CO mixed gas and confirmed a promoting effect from CO when its volume proportion in mixed gas is 20% at 850℃.The ReaxFF molecular dynamics(MD)simul...The experiment explored the Fe_(2)O_(3) reduction process with H_(2)/CO mixed gas and confirmed a promoting effect from CO when its volume proportion in mixed gas is 20% at 850℃.The ReaxFF molecular dynamics(MD)simulation method was used to observe the reduction process and provide an atomic-level explanation.The accuracy of the parameters used in the simulation was verified by the density functional theory(DFT)calculation.The simulation shows that the initial reduction rate of H_(2) is much faster than that of CO(from 800 to 950℃).As the reduction proceeds,cementite,obtained after CO participates in the reduction at 850℃,will appear on the iron surface.Due to the active properties of C atoms in cementite,they are easy to further react with the O atoms in Fe_(2)O_(3).The generation of internal CO may destroy the dense structure of the surface layer,thereby affecting the overall reduction swelling of Fe_(2)O_(3).However,excess CO is detrimental to the reaction rate,mainly because of the poor thermodynamic conditions of CO in the temperature range and the molecular diffusion capacity is not as good as that of H_(2).Furthermore,the surface structures obtained after H_(2) and CO reduction have been compared,and it was found that the structure obtained by CO reduction has a larger surface area,thus promoting the sub sequent reaction of H_(2).展开更多
Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies ...Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies between 1 keV and 150 keV.The results indicate that a smaller grain size leads to more defects forming in grain boundary regions during cascade processes.The impact of high-energy PKA may cause a certain degree of distortion of the grain boundaries,which has a higher probability in systems with smaller grain sizes and becomes more pronounced as the PKA energy increases.The direction of PKA can affect the formation and diffusion pathways of defects.When the PKA direction is perpendicular to the grain boundary,defects preferentially form near the grain boundary regions;by contrast,defects are more inclined to form in the interior of the grains.These results are of great significance for comprehending the changes in the performance of polycrystalline W under the high-energy fusion environments and can provide theoretical guidance for further optimization and application of W-based plasma materials.展开更多
The multi-scale modeling combined with the cohesive zone model(CZM)and the molecular dynamics(MD)method were preformed to simulate the crack propagation in NiTi shape memory alloys(SMAs).The metallographic microscope ...The multi-scale modeling combined with the cohesive zone model(CZM)and the molecular dynamics(MD)method were preformed to simulate the crack propagation in NiTi shape memory alloys(SMAs).The metallographic microscope and image processing technology were employed to achieve a quantitative grain size distribution of NiTi alloys so as to provide experimental data for molecular dynamics modeling at the atomic scale.Considering the size effect of molecular dynamics model on material properties,a reasonable modeling size was provided by taking into account three characteristic dimensions from the perspective of macro,meso,and micro scales according to the Buckinghamπtheorem.Then,the corresponding MD simulation on deformation and fracture behavior was investigated to derive a parameterized traction-separation(T-S)law,and then it was embedded into cohesive elements of finite element software.Thus,the crack propagation behavior in NiTi alloys was reproduced by the finite element method(FEM).The experimental results show that the predicted initiation fracture toughness is in good agreement with experimental data.In addition,it is found that the dynamics initiation fracture toughness increases with decreasing grain size and increasing loading velocity.展开更多
The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments...The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments and molecular dynamics(MD)simulations,this study investigates the microscopic enhanced oil recovery(EOR)mechanisms underlying residual oil removal using hybrid CO_(2) thermal systems.Based on the experimental models for the occurrence of heavy oil,this study evaluates the performance of hybrid CO_(2) thermal systems under various conditions using MD simulations.The results demonstrate that introducing CO_(2) molecules into heavy oil can effectively penetrate and decompose dense aggregates that are originally formed on hydrophobic surfaces.A stable miscible hybrid CO_(2) thermal system,with a high effective distribution ratio of CO_(2),proficiently reduces the interaction energies between heavy oil and rock surfaces,as well as within heavy oil.A visualization analysis of the interactions reveals that strong van der Waals(vdW)attractions occur between CO_(2) and heavy oil molecules,effectively promoting the decomposition and swelling of heavy oil.This unlocks the residual oil on the hydrophobic surfaces.Considering the impacts of temperature and CO_(2) concentration,an optimal gas-to-steam injection ratio(here,the CO_(2):steam ratio)ranging between 1:6 and 1:9 is recommended.This study examines the microscopic mechanisms underlying the hybrid CO_(2) thermal technique at a molecular scale,providing a significant theoretical guide for its expanded application in EOR.展开更多
The formation of donut-shaped penetration pore upon membrane fusion in a closed lipid membrane system is of biological significance,since such the structures extensively exist in living body with various functions.How...The formation of donut-shaped penetration pore upon membrane fusion in a closed lipid membrane system is of biological significance,since such the structures extensively exist in living body with various functions.However,the related formation dynamics is unclear because of the limitation of experimental techniques.This work developed a new model of intra-vesicular fusion to elaborate the formation and stabilization of penetration pores by employing molecular dynamics simulations,based on simplified spherical lipid vesicle system,and investigated the regulation of membrane lipid composition.Results showed that penetration pore could be successfully formed based on the strategy of membrane fusion.The ease of intra-vesicular fusion and penetration pore formation was closely correlated with the lipid curvature properties,where negative spontaneous curvature of lipids seemed to be unfavorable for intra-vesicle fusion.Furthermore,the inner membrane tension around the pore was much larger than other regions,which governed the penetration pore size and stability.This work provided basic understanding for vesicle penetration pore formation and stabilization mechanisms.展开更多
The effects of temperature and Re content on the mechanical properties,dislocation morphology,and deformation mechanism of γ-γ′phases nickel-based single crystal superalloys are investigated by using the molecular ...The effects of temperature and Re content on the mechanical properties,dislocation morphology,and deformation mechanism of γ-γ′phases nickel-based single crystal superalloys are investigated by using the molecular dynamics method through the model of γ-γ′phases containing hole defect.The addition of Re makes the dislocation distribution tend towards the γ phase.The higher the Re content,the earlier theγphase yields,while the γ′phase yields later.Dislocation bends under the combined action of the applied force and the resistance of the Re atoms to form a bend point.The Re atoms are located at the bend points and strengthen the alloy by fixing the dislocation and preventing it from cutting the γ′phase.Dislocations nucleate first in the γ phase,causing theγphase to deform plastically before the γ′phase.As the strain increases,the dislocation length first remains unchanged,then increases rapidly,and finally fluctuates and changes.The dislocation lengths in the γ phase are larger than those in the γ′phase at different temperatures.The dislocation length shows a decreasing tendency with the increase of the temperature.Temperature can affect movement of the dislocation,and superalloys have different plastic deformation mechanisms at low,medium and high temperatures.展开更多
Seismic quantitative reservoir simulations and characterizations have played a vital role in exploring stratigraphic traps,such as lateaggradational lowstands prograding wedge systems(LPWS)within lowstands systems tra...Seismic quantitative reservoir simulations and characterizations have played a vital role in exploring stratigraphic traps,such as lateaggradational lowstands prograding wedge systems(LPWS)within lowstands systems tracts(LST).However,seismic data acquisition operations are always dominated by exceptional seismic coherent noise events,e.g.,multiples,which reduce the signal strengths of the sourcegenerated incident seismic waves within vertically and laterally heterogeneous earth systems.Hence,these noise events create hurdles in predicting paleo-depositional impedance(PDI),paleo-thickness(PTS),paleo-dense fractured networks,erosional and depositional zones,faultcontrolled migrations,and types of seismic reflection configurations(SRFC),which are key elements in developing stratigraphic pinch-out traps.This research utilizes the state-of-the-art technologies of spectral wavelet-based instantaneous time-frequency analysis and seismic waveform frequency-controlled porosity-constrained static reservoir simulation(FDPVS)tools to quantify the LPWS inside the Onshore Basin,Pakistan.The use of conventional amplitude-based seismic attributes,such as the average energy,remained a better tool for deciphering the overall geological architecture of the LPWS.Conventional FDPVS realizations resolved a PDI of−1.391 gm./c.c.^(*)m/s to−0.97 gm./c.c.^(*)m/s for LPWS with PTS of 12 and 20 m,respectively.A 0.9 km lateral extent of paleo-dense fractured networks(PDFN)with a strong linear regression R^(2)=0.93 was also resolved.Average energy attribute-based instantaneous frequency FDPVS realizations enabled the imaging of parallel-toprograding SRFC with resolved magnitudes of−0.259 gm./c.c.^(*)m/s for PDI,20 m for PTS,and 0.73 km for PDFN with linear regression transforms at R^(2)=0.92,which indicates the deposition of onlap fill facies inside the LPWS during extensive sea-level fall.These realizations have also resolved frequency-controlled fault migrations on 27-Hz spectral waveform-based amplitude plots with 2.174 gm./c.c.^(*)m/s PDI for conduit fault systems and 27-Hz with 0.585 gm./c.c.^(*)m/s PDI for sealing fault systems.All these structural configurations are completely sealed up by transgressive seals of transgressive systems tracts and,hence,developed into pure stratigraphic-based oil and gas plays.This research has strong implications for side-tracking drilling locations and provides an analogue for basins with similar geology and stratigraphy worldwide.展开更多
In the domain of high-performance engineering polymers, the enhancement of mechanical flexibility in poly(phenylene sulfide) (PPS) resins has long posed a significant challenge. A novel molecular structure, designated...In the domain of high-performance engineering polymers, the enhancement of mechanical flexibility in poly(phenylene sulfide) (PPS) resins has long posed a significant challenge. A novel molecular structure, designated as PP-He-IS, wherein imide rings and an aliphatic hexylene chain are covalently incorporated into the PPS backbone to enhance its flexibility, is introduced in this study. Molecular dynamics (MD) simulations are employed to systematically explore the effects of diversifying the backbone chain structures by substituting phenyl units with alkyl chains of varying lengths, referred to as PP-A-IS where “A” signifies the distinct intermediary alkyl chain configurations. Computational analyses reveal a discernable decrement in the glass transition temperature (Tg) and elastic modulus, counterbalanced by an increment in yield strength as the alkyl chain length is extended. Notably, the PP-He-IS variant is shown to exhibit superior yield strength while simultaneously maintaining reduced elastic modulus and Tg values, positioning it as an advantageous candidate for flexible PPS applications. Mesoscopic analyses further indicate that structures such as PP-He-IS, PP-Pe-IS, and PP-Bu-IS manifest remarkable flexibility, attributable to the presence of freely rotatable carbon-carbon single bonds. Experimental validation confirms that a melting temperature of 504 K which is lower than that of conventional PPS, and lower crystallinity are exhibited by PP-He-IS, thereby affording enhanced processability without compromising inherent thermal stability. Novel insights into the strategic modification of PPS for mechanical flexibility are thus furnished by this study, which also accentuates the pivotal role played by molecular dynamics simulations in spearheading high-throughput investigations in polymer material modifications.展开更多
Graphene aerogel(GA),as a novel solid material,has shown great potential in engineering applications due to its unique mechanical properties.In this study,the mechanical performance of GA under high-velocity projectil...Graphene aerogel(GA),as a novel solid material,has shown great potential in engineering applications due to its unique mechanical properties.In this study,the mechanical performance of GA under high-velocity projectile impacts is thoroughly investigated using full-atomic molecular dynamics(MD)simulations.The study results show that the porous structure and density are key factors determining the mechanical response of GA under impact loading.Specifically,the impact-induced penetration of the projectile leads to the collapse of the pore structure,causing stretching and subsequent rupture of covalent bonds in graphene sheets.Moreover,the effects of temperature on the mechanical performance of GA have been proven to be minimal,thereby highlighting the mechanical stability of GA over a wide range of temperatures.Finally,the energy absorption density(EAD)and energy absorption efficiency(EAE)metrics are adopted to assess the energy absorption capacity of GA during projectile penetration.The research findings of this work demonstrate the significant potential of GA for energy absorption applications.展开更多
Single-phase concentrated solid solution alloys(SP-CSAs),including high-entropy alloys,have received extensive attention due to their excellent irradiation resistance.In this work,displacement cascade simulations are ...Single-phase concentrated solid solution alloys(SP-CSAs),including high-entropy alloys,have received extensive attention due to their excellent irradiation resistance.In this work,displacement cascade simulations are conducted using the molecular dynamics method to study the evolution of defects in Ni-based SP-CSAs.Compared with pure Ni,the NiCr,NiCo,and NiCu alloys exhibit a larger number of Frankel pairs(FPs)in the thermal peak stage,but a smaller number of surviving FPs.However,the NiFe alloy displays the opposite phenomenon.To explain these different observations for NiFe and other alloys,the formation energy and migration energy of interstitials/vacancies are calculated.In the NiFe alloy,both the formation energy and migration energy barrier are higher.On the other hand,in NiCr and other alloys,the formation energy of interstitials/vacancies is lower,as is the migration energy barrier of interstitials.The energy analysis agrees well with previous observations.The present work provides new insights into the mechanism behind the irradiation resistance of binary Ni-based SP-CSAs.展开更多
Elevated O-GlcNAcylation has been shown to be closely correlated with the occurrence and development of cancer,and inhibiting O-GlcNAc transferase(OGT)activity was demonstrated as a potential tumor treatment strategy....Elevated O-GlcNAcylation has been shown to be closely correlated with the occurrence and development of cancer,and inhibiting O-GlcNAc transferase(OGT)activity was demonstrated as a potential tumor treatment strategy.However,the development of pharmacological OGT inhibitors still faces challenges,such as low affinity and poor selectivity.Consider-ing to OGT preferences for the sequence of its peptidic substrates,we herein integrated molecular dynamics simulation approaches to give deep insights into the binding behaviors between OGT and its peptidic substrate ZO3S1,and discussed the unfavorable inter-residue contacts inside the binding pocket,especially between H509 of OGT and S15 of the peptide,upon temperature increase.Removing this unfavorable contact from the peptide(ZO3S1 with S15A mutation)was shown to be able to increase its interaction with OGT,which was manifested by the enhanced OGT activity against this peptide.The pseudo-substrate peptide(ZO3S1 with S13A and S15A mutations)inhibited the activity of purified OGT with an IC_(50)of 192.9μM and it can also inhibit the total O-GlcNAcylation in cancer cell lines in a concentration-dependent manner.Our results provided useful models and basis for further rational optimization of selective OGT inhibitors based on the dynamic interactions of OGT and its peptidic substrates.展开更多
This study investigates the mechanism by which baicalin inhibits cancer cell growth through estrogen receptor 1 (ESR1) using molecular dynamics simulations. The results show that baicalin primarily binds to the ligand...This study investigates the mechanism by which baicalin inhibits cancer cell growth through estrogen receptor 1 (ESR1) using molecular dynamics simulations. The results show that baicalin primarily binds to the ligand-binding domain (LBD) of ESR1, interacting through hydrogen bonds and hydrophobic interactions. After binding, the overall and local conformations of ESR1 change, affecting its interactions with other proteins and thus modulating the signaling pathways of cancer cells. Binding free energy analysis indicates that the binding of baicalin to ESR1 is spontaneous and relatively stable. Additionally, baicalin can inhibit the binding of ESR1 to estrogen, blocking the estrogen signaling pathway and thereby suppressing the growth and proliferation of cancer cells. This study provides theoretical and experimental foundations for the potential use of baicalin as an anticancer drug, offering new insights and methods for the development of novel anticancer drugs. However, the study has some limitations, such as limited simulation time and simplified systems. Future research can extend the simulation time and consider more physiological factors to more accurately simulate the interactions between baicalin and ESR1.展开更多
We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresp...We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresponding extended ab initio data set,we construct interpolation formulas covering the range from low-density,high-temperature to high-density,low-temperature plasmas.Our conductivity model repro-duces the well-known limits of the Spitzer and Ziman theory.We compare with available experimental data andfind very good agreement.The new conductivity model can be applied,for example,in dynamo simulations for magneticfield generation in gas giant planets,brown dwarfs,and stellar envelopes.展开更多
基金the National Basic Research Program of China under contract Nos 2013CB956501 and 2012CB956103
文摘Abundant evidences of higher sea levels from Jiangsu and Fujian coasts have proved a marine transgression event during 30–40 ka BP, suggesting that there was a stage with high sea level and a warm climate when ice sheets shrank in the Northern Hemisphere. The duration of 30–40 ka BP spanned a period in the late Marine Isotope Stage 3（MIS 3） and was in nature an interstadial epoch during the Last Glacial period of the Quaternary. Different from the glacial period with a cold climate, this marine transgression considered as a penultimate higher sea level during the Quaternary remains a puzzle that why the evidence is contrary to the Quaternary glacial theory. It is important to understand sea level rise for these areas sensitively responding to the global changes in the future. To recognize the key issues on sea level changes, the eustatic sea level（H_S） was defined as the glaciation-climateforced sea levels, and the relative sea level change（H_R） was defined as that a sea level record was preserved in sediment that experienced multiple secondary actions of land and sea effects. On the basis as defined above, we constructed multi-level models of climate-driven glacio-eustatic changes and land-sea systems. By integrating data sets from eight borehole cores and prescribing the boundary conditions, we simulated the changes of HS and HR in the East China Sea and southern Yellow Sea areas in the late MIS 3. The marine transgression strata from the borehole core data was identified at ca. 30 m below present sea level as a result of the collective influence of ice melting water, neotectonic subsidence, sediment compaction and terrestrial sediment filling since ca. 35 ka ago,whereas the simulated relative sea-levels turned out to be –26.3––29.9 m a.s.l. The small error involved in the simulation results of ±（2.5–4.5） m demonstrated the credibility of the results. Our results indicated that sea level change in the late MIS 3 was dominated by glacial effects, in which the eustatic sea-level was between –19.2––22.1m a.s.l. The study sheds light on the nature of sea-level changes along the east coast of China in the late MIS 3 and contributes to understanding the characteristics of marine transgression under the effects of multiple complex land-sea interactions.
基金supported by grants from the National Science Foundation of China(Grant Nos.11774272,and 12075171)。
文摘Structural elasticity of double-strand DNAs is very important for their biological functions such as DNA-ligand binding and DNA-protein recognition.By all-atom molecular dynamics simulations,we investigated the bending elasticity of DNA with three typical sequences including poly(A)-poly(T)(AA-TT),poly(AT)-poly(TA)(AT-TA),and a generic sequence(GENE).Our calculations indicate that,AA-TT has an apparently larger bending persistence length(P~63 nm)than GENE(P~49 nm)and AT-TA(P~48 nm)while the persistence length of AT-TA is only very slightly smaller than that of GENE,which agrees well with those from existing works.Moreover,through extensive electrostatic calculations,we found that the sequence-dependent bending elasticity is attributed to the sequence-dependent electrostatic bending energy for AA-TT,AT-TA and GENE,which is coupled to their backbone structures.Particularly,the apparently stronger bending stiffness of AA-TT is attributed to its narrower minor groove.Interestingly,for the three DNAs,we predicted the non-electrostatic persistence length of~17 nm,thus electrostatic interaction makes the major contribution to DNA bending elasticity.The mechanism of electrostatic energy dominating sequence effect in DNA bending elasticity is furtherly illustrated through the electrostatic calculations for a grooved coarse-grained DNA model where minor groove width and other microscopic structural parameters can be artificially adjusted.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11504384 and 11121403computational resources provided by Supercomputing Center of Chinese Academy of Sciences(SCCAS)
文摘The lubrication characteristics of liquid crystal(LC) molecules sheared between two crystalline surfaces obtained from molecular dynamics(MD) simulations are reported in this article.We consider a coarse-grained rigid bead-necklace model of the LC molecules confined between two atomic surfaces subject to different shearing velocities.A systematic study shows that the slip length of LC lubrication changes significantly as a function of the LC-surface interaction energy,which can be well described though a theoretical curve.The slip length increases as shear rate increases at high LC-surface interaction energy.However,this trend can not be observed for low interaction energy.The orientation of the LC molecules near the surface is found to be guided by the atomics surfaces.The influence of temperature on the lubrication characteristics is also discussed in this article.
基金supported by the National Natural Science Foundation of China(No.21973064)the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2021HXBH017)。
文摘Protein-protein interactions are vital for a wide range of biological processes.The interactions between the hypoxia-inducible factor and von Hippel Lindau(VHL)are attractive drug targets for ischemic heart disease.In order to disrupt this interaction,the strategy to target VHL binding site using a hydroxyproline-like(pro-like)small molecule has been reported.In this study,we focused on the inhibition mechanism between the pro-like inhibitors and the VHL protein,which were investigated via molecular dynamics simulations and binding free energy calculations.It was found that pro-like inhibitors showed a strong binding affinity toward VHL.Binding free energy calculations and free energy decompositions suggested that the modification of various regions of pro-like inhibitors may provide useful information for future drug design.
基金supported by the Science and Technology Research Project from Education Department of Jilin Province (No. JJKH20231296KJ)the Natural Science Foundation of Science and Technology Department of Jilin Province (Joint Fund Project) (No. YDZJ202201ZYTS340)+9 种基金the Fundamental Research Funds for the Central Universities (No. 2412022ZD013)the Science and Technology Development Plan Project of Jilin Province (Nos. SKL202302030, SKL202402017, 20210204126YY, 20230204113YY, 20240602003RC, 20210402059GH)the National Natural Science Foundation of China (Nos. 22174137, 22322410, 92372102 and 22073094)the Cooperation Funding of Changchun with Chinese Academy of Sciences (No. 22SH13)the Capital Construction Fund Projects within the Budget of Jilin Province (No. 2023C042–5)the University Level Scientific Research Projects of Ordinary Universities in Xinjiang Uygur Autonomous Region (No. 2022YQSN002)the State Key Laboratory of Molecular Engineering of Polymers (Fudan University) (No. K2024–11)the Program for Young Scholars in Regional Development of CASthe essential support of the Network and Computing Center, CIAC, CASthe Computing Center of Jilin Province。
文摘Recent advancements in nanotechnology have spotlighted the catalytic potential of nanozymes, particularly single-atom nanozymes(SANs), which are pivotal for innovations in biosensing and medical diagnostics. Among others, DNA stands out as an ideal biological regulator. Its inherent programmability and interaction capabilities allow it to significantly modulate nanozyme activity. This study delves into the dynamic interplay between DNA and molybdenum-zinc single-atom nanozymes(Mo-Zn SANs). Using molecular dynamics simulations, we uncover how DNA influences the peroxidase-like activities of Mo-Zn SANs, providing a foundational understanding that broadens the application scope of SANs in biosensing.With these insights as a foundation, we developed and demonstrated a model aptasensor for point-ofcare testing(POCT), utilizing a label-free colorimetric approach that leverages DNA-nanozyme interactions to achieve high-sensitivity detection of lysozyme. Our work elucidates the nuanced control DNA exerts over nanozyme functionality and illustrates the application of this molecular mechanism through a smartphone-assisted biosensing platform. This study not only underscores the practical implications of DNA-regulated Mo-Zn SANs in enhancing biosensing platforms, but also highlights the potential of single-atom nanozyme technology to revolutionize diagnostic tools through its inherent versatility and sensitivity.
基金supported by the Natural Science Foundation of Hebei Province(E2024209052)the Youth Scholars Promotion Plan of North China University of Science and Technology(QNTJ202307).
文摘Eutectic high entropy alloys are noted for their excellent castability and comprehensive mechanical properties.The excellent mechanical properties are closely related to the activation and evolution of deformation mechanisms at the atomic scale.In this work,AlCoCrFeNi2.1 alloy is taken as the research object.The mechanical behaviors and deformation mechanisms of the FCC and B2 single crystals with different orientations and the FCC/B2 composites with K-S orientation relationship during nanoindentation processes are systematically studied by molecular dynamics simulations.The results show that the mechanical behaviors of FCC single crystals are significantly orientation-dependent,meanwhile,the indentation force of[110]single crystal is the lowest at the elastic-plastic transition point,and that for[100]single crystal is the lowest in plastic deformation stage.Compared with FCC,the stress for B2 single crystals at the elastic-plastic transition point is higher.However,more deformation systems such as stacking faults,twins and dislocation loops are activated in FCC single crystal during the plastic deformation process,resulting in higher indentation force.For composites,the flow stress increases with the increase of B2 phase thickness during the initial stage of deformation.When indenter penetrates heterogeneous interface,the significantly increased deformation system in FCC phase leads to a significant increase in indentation force.The mechanical behaviors and deformation mechanisms depend on the component single crystal.When the thickness of the component layer is less than 15 nm,the heterogeneous interfaces fail to prevent the dislocation slip and improve the indentation force.The results will enrich the plastic deformation mechanisms of multi-principal eutectic alloys and provide guidance for the design of nanocrystalline metallic materials.
基金Project supported by the National Natural Science Foundation of China (Grant No. 52271105)。
文摘Uranium–molybdenum(U–Mo) alloys are critical for nuclear power generation and propulsion because of their superior thermal conductivity, irradiation stability, and anti-swelling properties. This study explores the plastic deformation mechanisms of γ-phase U–Mo alloys using molecular dynamics(MD) simulations. In the slip model, the generalized stacking fault energy(GSFE) and the modified Peierls–Nabarro(P–N) model are used to determine the competitive relationships among different slip systems. In the twinning model, the generalized plane fault energy(GPFE) is assessed to evaluate the competition between slip and twinning. The findings reveal that among the three slip systems, the {110}<111>slip system is preferentially activated, while in the {112}<111> system, twinning is favored over slip, as confirmed by MD tensile simulations conducted in various directions. Additionally, the impact of Mo content on deformation behavior is emphasized. Insights are provided for optimizing process conditions to avoid γ → α′′ transitions, thereby maintaining a higher proportion of γ-phase U–Mo alloys for practical applications.
基金financial support from the National Natural Science Foundation of China(Nos.52204335 and 52374319)the National Nature Science Foundation of China(No.52174291)the Central Universities Foundation of China(No.06500170)。
文摘The experiment explored the Fe_(2)O_(3) reduction process with H_(2)/CO mixed gas and confirmed a promoting effect from CO when its volume proportion in mixed gas is 20% at 850℃.The ReaxFF molecular dynamics(MD)simulation method was used to observe the reduction process and provide an atomic-level explanation.The accuracy of the parameters used in the simulation was verified by the density functional theory(DFT)calculation.The simulation shows that the initial reduction rate of H_(2) is much faster than that of CO(from 800 to 950℃).As the reduction proceeds,cementite,obtained after CO participates in the reduction at 850℃,will appear on the iron surface.Due to the active properties of C atoms in cementite,they are easy to further react with the O atoms in Fe_(2)O_(3).The generation of internal CO may destroy the dense structure of the surface layer,thereby affecting the overall reduction swelling of Fe_(2)O_(3).However,excess CO is detrimental to the reaction rate,mainly because of the poor thermodynamic conditions of CO in the temperature range and the molecular diffusion capacity is not as good as that of H_(2).Furthermore,the surface structures obtained after H_(2) and CO reduction have been compared,and it was found that the structure obtained by CO reduction has a larger surface area,thus promoting the sub sequent reaction of H_(2).
基金Project supported by the National MCF Energy Research and Development Program of China(Grant No.2018YFE0308101)the National Key Research and Development Program of China(Grant No.2018YFB0704000)+1 种基金the Suqian Science and Technology Program(Grant No.K202337)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.23KJD490001).
文摘Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies between 1 keV and 150 keV.The results indicate that a smaller grain size leads to more defects forming in grain boundary regions during cascade processes.The impact of high-energy PKA may cause a certain degree of distortion of the grain boundaries,which has a higher probability in systems with smaller grain sizes and becomes more pronounced as the PKA energy increases.The direction of PKA can affect the formation and diffusion pathways of defects.When the PKA direction is perpendicular to the grain boundary,defects preferentially form near the grain boundary regions;by contrast,defects are more inclined to form in the interior of the grains.These results are of great significance for comprehending the changes in the performance of polycrystalline W under the high-energy fusion environments and can provide theoretical guidance for further optimization and application of W-based plasma materials.
基金Funded by the National Natural Science Foundation of China Academy of Engineering Physics and Jointly Setup"NSAF"Joint Fund(No.U1430119)。
文摘The multi-scale modeling combined with the cohesive zone model(CZM)and the molecular dynamics(MD)method were preformed to simulate the crack propagation in NiTi shape memory alloys(SMAs).The metallographic microscope and image processing technology were employed to achieve a quantitative grain size distribution of NiTi alloys so as to provide experimental data for molecular dynamics modeling at the atomic scale.Considering the size effect of molecular dynamics model on material properties,a reasonable modeling size was provided by taking into account three characteristic dimensions from the perspective of macro,meso,and micro scales according to the Buckinghamπtheorem.Then,the corresponding MD simulation on deformation and fracture behavior was investigated to derive a parameterized traction-separation(T-S)law,and then it was embedded into cohesive elements of finite element software.Thus,the crack propagation behavior in NiTi alloys was reproduced by the finite element method(FEM).The experimental results show that the predicted initiation fracture toughness is in good agreement with experimental data.In addition,it is found that the dynamics initiation fracture toughness increases with decreasing grain size and increasing loading velocity.
基金financially supported by the National Natural Science Foundation of China(No.U20B6003)the China Scholarship Council(No.202306440015)a project of the China Petroleum&Chemical Corporation(No.P22174)。
文摘The hybrid CO_(2) thermal technique has achieved considerable success globally in extracting residual heavy oil from reserves following a long-term steam stimulation process.Using microscopic visualization experiments and molecular dynamics(MD)simulations,this study investigates the microscopic enhanced oil recovery(EOR)mechanisms underlying residual oil removal using hybrid CO_(2) thermal systems.Based on the experimental models for the occurrence of heavy oil,this study evaluates the performance of hybrid CO_(2) thermal systems under various conditions using MD simulations.The results demonstrate that introducing CO_(2) molecules into heavy oil can effectively penetrate and decompose dense aggregates that are originally formed on hydrophobic surfaces.A stable miscible hybrid CO_(2) thermal system,with a high effective distribution ratio of CO_(2),proficiently reduces the interaction energies between heavy oil and rock surfaces,as well as within heavy oil.A visualization analysis of the interactions reveals that strong van der Waals(vdW)attractions occur between CO_(2) and heavy oil molecules,effectively promoting the decomposition and swelling of heavy oil.This unlocks the residual oil on the hydrophobic surfaces.Considering the impacts of temperature and CO_(2) concentration,an optimal gas-to-steam injection ratio(here,the CO_(2):steam ratio)ranging between 1:6 and 1:9 is recommended.This study examines the microscopic mechanisms underlying the hybrid CO_(2) thermal technique at a molecular scale,providing a significant theoretical guide for its expanded application in EOR.
基金supported by the National Natural Science Foundation of China(Grants Nos.T2394512,32130061,and 12172366)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.GJJSTD20220002).
文摘The formation of donut-shaped penetration pore upon membrane fusion in a closed lipid membrane system is of biological significance,since such the structures extensively exist in living body with various functions.However,the related formation dynamics is unclear because of the limitation of experimental techniques.This work developed a new model of intra-vesicular fusion to elaborate the formation and stabilization of penetration pores by employing molecular dynamics simulations,based on simplified spherical lipid vesicle system,and investigated the regulation of membrane lipid composition.Results showed that penetration pore could be successfully formed based on the strategy of membrane fusion.The ease of intra-vesicular fusion and penetration pore formation was closely correlated with the lipid curvature properties,where negative spontaneous curvature of lipids seemed to be unfavorable for intra-vesicle fusion.Furthermore,the inner membrane tension around the pore was much larger than other regions,which governed the penetration pore size and stability.This work provided basic understanding for vesicle penetration pore formation and stabilization mechanisms.
基金Project supported by the Xi’an Science and Technology Plan Project of Shaanxi Province of China(Grant No.23GXFW0086).
文摘The effects of temperature and Re content on the mechanical properties,dislocation morphology,and deformation mechanism of γ-γ′phases nickel-based single crystal superalloys are investigated by using the molecular dynamics method through the model of γ-γ′phases containing hole defect.The addition of Re makes the dislocation distribution tend towards the γ phase.The higher the Re content,the earlier theγphase yields,while the γ′phase yields later.Dislocation bends under the combined action of the applied force and the resistance of the Re atoms to form a bend point.The Re atoms are located at the bend points and strengthen the alloy by fixing the dislocation and preventing it from cutting the γ′phase.Dislocations nucleate first in the γ phase,causing theγphase to deform plastically before the γ′phase.As the strain increases,the dislocation length first remains unchanged,then increases rapidly,and finally fluctuates and changes.The dislocation lengths in the γ phase are larger than those in the γ′phase at different temperatures.The dislocation length shows a decreasing tendency with the increase of the temperature.Temperature can affect movement of the dislocation,and superalloys have different plastic deformation mechanisms at low,medium and high temperatures.
文摘Seismic quantitative reservoir simulations and characterizations have played a vital role in exploring stratigraphic traps,such as lateaggradational lowstands prograding wedge systems(LPWS)within lowstands systems tracts(LST).However,seismic data acquisition operations are always dominated by exceptional seismic coherent noise events,e.g.,multiples,which reduce the signal strengths of the sourcegenerated incident seismic waves within vertically and laterally heterogeneous earth systems.Hence,these noise events create hurdles in predicting paleo-depositional impedance(PDI),paleo-thickness(PTS),paleo-dense fractured networks,erosional and depositional zones,faultcontrolled migrations,and types of seismic reflection configurations(SRFC),which are key elements in developing stratigraphic pinch-out traps.This research utilizes the state-of-the-art technologies of spectral wavelet-based instantaneous time-frequency analysis and seismic waveform frequency-controlled porosity-constrained static reservoir simulation(FDPVS)tools to quantify the LPWS inside the Onshore Basin,Pakistan.The use of conventional amplitude-based seismic attributes,such as the average energy,remained a better tool for deciphering the overall geological architecture of the LPWS.Conventional FDPVS realizations resolved a PDI of−1.391 gm./c.c.^(*)m/s to−0.97 gm./c.c.^(*)m/s for LPWS with PTS of 12 and 20 m,respectively.A 0.9 km lateral extent of paleo-dense fractured networks(PDFN)with a strong linear regression R^(2)=0.93 was also resolved.Average energy attribute-based instantaneous frequency FDPVS realizations enabled the imaging of parallel-toprograding SRFC with resolved magnitudes of−0.259 gm./c.c.^(*)m/s for PDI,20 m for PTS,and 0.73 km for PDFN with linear regression transforms at R^(2)=0.92,which indicates the deposition of onlap fill facies inside the LPWS during extensive sea-level fall.These realizations have also resolved frequency-controlled fault migrations on 27-Hz spectral waveform-based amplitude plots with 2.174 gm./c.c.^(*)m/s PDI for conduit fault systems and 27-Hz with 0.585 gm./c.c.^(*)m/s PDI for sealing fault systems.All these structural configurations are completely sealed up by transgressive seals of transgressive systems tracts and,hence,developed into pure stratigraphic-based oil and gas plays.This research has strong implications for side-tracking drilling locations and provides an analogue for basins with similar geology and stratigraphy worldwide.
文摘In the domain of high-performance engineering polymers, the enhancement of mechanical flexibility in poly(phenylene sulfide) (PPS) resins has long posed a significant challenge. A novel molecular structure, designated as PP-He-IS, wherein imide rings and an aliphatic hexylene chain are covalently incorporated into the PPS backbone to enhance its flexibility, is introduced in this study. Molecular dynamics (MD) simulations are employed to systematically explore the effects of diversifying the backbone chain structures by substituting phenyl units with alkyl chains of varying lengths, referred to as PP-A-IS where “A” signifies the distinct intermediary alkyl chain configurations. Computational analyses reveal a discernable decrement in the glass transition temperature (Tg) and elastic modulus, counterbalanced by an increment in yield strength as the alkyl chain length is extended. Notably, the PP-He-IS variant is shown to exhibit superior yield strength while simultaneously maintaining reduced elastic modulus and Tg values, positioning it as an advantageous candidate for flexible PPS applications. Mesoscopic analyses further indicate that structures such as PP-He-IS, PP-Pe-IS, and PP-Bu-IS manifest remarkable flexibility, attributable to the presence of freely rotatable carbon-carbon single bonds. Experimental validation confirms that a melting temperature of 504 K which is lower than that of conventional PPS, and lower crystallinity are exhibited by PP-He-IS, thereby affording enhanced processability without compromising inherent thermal stability. Novel insights into the strategic modification of PPS for mechanical flexibility are thus furnished by this study, which also accentuates the pivotal role played by molecular dynamics simulations in spearheading high-throughput investigations in polymer material modifications.
基金supported by the National Natural Science Foundation of China(No.12102256).
文摘Graphene aerogel(GA),as a novel solid material,has shown great potential in engineering applications due to its unique mechanical properties.In this study,the mechanical performance of GA under high-velocity projectile impacts is thoroughly investigated using full-atomic molecular dynamics(MD)simulations.The study results show that the porous structure and density are key factors determining the mechanical response of GA under impact loading.Specifically,the impact-induced penetration of the projectile leads to the collapse of the pore structure,causing stretching and subsequent rupture of covalent bonds in graphene sheets.Moreover,the effects of temperature on the mechanical performance of GA have been proven to be minimal,thereby highlighting the mechanical stability of GA over a wide range of temperatures.Finally,the energy absorption density(EAD)and energy absorption efficiency(EAE)metrics are adopted to assess the energy absorption capacity of GA during projectile penetration.The research findings of this work demonstrate the significant potential of GA for energy absorption applications.
基金supported by the National Natural Science Foundation of China(12232008,12072211)Foundation of Key laboratory(2022JCJQLB05703)Sichuan Province Science and Technology Project(2023NSFSC0914,2020JDJQ0029).
文摘Single-phase concentrated solid solution alloys(SP-CSAs),including high-entropy alloys,have received extensive attention due to their excellent irradiation resistance.In this work,displacement cascade simulations are conducted using the molecular dynamics method to study the evolution of defects in Ni-based SP-CSAs.Compared with pure Ni,the NiCr,NiCo,and NiCu alloys exhibit a larger number of Frankel pairs(FPs)in the thermal peak stage,but a smaller number of surviving FPs.However,the NiFe alloy displays the opposite phenomenon.To explain these different observations for NiFe and other alloys,the formation energy and migration energy of interstitials/vacancies are calculated.In the NiFe alloy,both the formation energy and migration energy barrier are higher.On the other hand,in NiCr and other alloys,the formation energy of interstitials/vacancies is lower,as is the migration energy barrier of interstitials.The energy analysis agrees well with previous observations.The present work provides new insights into the mechanism behind the irradiation resistance of binary Ni-based SP-CSAs.
基金supported by the National Natural Science Foundation of China(No.21907038)supported by the basic research program of Jiangnan university(No.JUSRP12016)the innovation and entrepreneurship program of Jiangsu province.
文摘Elevated O-GlcNAcylation has been shown to be closely correlated with the occurrence and development of cancer,and inhibiting O-GlcNAc transferase(OGT)activity was demonstrated as a potential tumor treatment strategy.However,the development of pharmacological OGT inhibitors still faces challenges,such as low affinity and poor selectivity.Consider-ing to OGT preferences for the sequence of its peptidic substrates,we herein integrated molecular dynamics simulation approaches to give deep insights into the binding behaviors between OGT and its peptidic substrate ZO3S1,and discussed the unfavorable inter-residue contacts inside the binding pocket,especially between H509 of OGT and S15 of the peptide,upon temperature increase.Removing this unfavorable contact from the peptide(ZO3S1 with S15A mutation)was shown to be able to increase its interaction with OGT,which was manifested by the enhanced OGT activity against this peptide.The pseudo-substrate peptide(ZO3S1 with S13A and S15A mutations)inhibited the activity of purified OGT with an IC_(50)of 192.9μM and it can also inhibit the total O-GlcNAcylation in cancer cell lines in a concentration-dependent manner.Our results provided useful models and basis for further rational optimization of selective OGT inhibitors based on the dynamic interactions of OGT and its peptidic substrates.
文摘This study investigates the mechanism by which baicalin inhibits cancer cell growth through estrogen receptor 1 (ESR1) using molecular dynamics simulations. The results show that baicalin primarily binds to the ligand-binding domain (LBD) of ESR1, interacting through hydrogen bonds and hydrophobic interactions. After binding, the overall and local conformations of ESR1 change, affecting its interactions with other proteins and thus modulating the signaling pathways of cancer cells. Binding free energy analysis indicates that the binding of baicalin to ESR1 is spontaneous and relatively stable. Additionally, baicalin can inhibit the binding of ESR1 to estrogen, blocking the estrogen signaling pathway and thereby suppressing the growth and proliferation of cancer cells. This study provides theoretical and experimental foundations for the potential use of baicalin as an anticancer drug, offering new insights and methods for the development of novel anticancer drugs. However, the study has some limitations, such as limited simulation time and simplified systems. Future research can extend the simulation time and consider more physiological factors to more accurately simulate the interactions between baicalin and ESR1.
基金supported by the Priority Program SPP 1992 of the German Science Foundation(DFG)The Diversity of Exoplanets under project number 362460292.
文摘We calculate the electrical and thermal conductivity of hydrogen for a wide range of densities and temperatures by using molecular dynamics simulations informed by density functional theory.On the basis of the corresponding extended ab initio data set,we construct interpolation formulas covering the range from low-density,high-temperature to high-density,low-temperature plasmas.Our conductivity model repro-duces the well-known limits of the Spitzer and Ziman theory.We compare with available experimental data andfind very good agreement.The new conductivity model can be applied,for example,in dynamo simulations for magneticfield generation in gas giant planets,brown dwarfs,and stellar envelopes.
