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
Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DN...Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.展开更多
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic t...Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic target for cancer. However, a major problem of current MTHFD2 inhibitors is their lack of selectivity and reactivity with its closest isoform, MTHFD1. Recently, the first selective MTHFD2 inhibitor, DS44960156, has been reported and it exhibits a more than 18-fold selectivity for MTHFD2 over MTHFD1. However, mechanism of DS44960156 selective binding to MTHFD2 over MTHFD1 is unknown. In this study, molecular docking, molecular dynamics (MD) simulations, molecular mechanics generalized born/surface area (MM_GBSA) binding free energy calculations, and analysis of the decomposition of binding free energies were used to investigate the selective binding mechanism of DS44960156 to the folate-binding site of MTHFD2 over MTHFD1. The results revealed that contributions from residues Gln100/Gln132, Val55/Asn87, and Gly237/Gly310 in the binding pocket of MTHFD1/MTHFD2 are the key factors responsible for the binding selectivity. These findings explain the selectivity of DS44960156 to MTHFD2 over MTHFD1, and may provide guidance for the future study and design of novel MTHFD2 inhibitors.展开更多
The investigation results of the bonding structure of CaO-SiO2 slag by means of molecular dynamics simulation are presented. The characteristics of partial radial distribution function gij(r) are in good agreement wit...The investigation results of the bonding structure of CaO-SiO2 slag by means of molecular dynamics simulation are presented. The characteristics of partial radial distribution function gij(r) are in good agreement with the measurement of X-ray diffraction, and the variation of Qn with different SiO4 tetrahedra following the change of Xcao is consistent with the results of Raman spectroscopy, The partial vibrational density of states Fsi(ω) shows that two bands appear in the range of 636-737 cm-1 and 800? 200 cm-1 respectively which are also consistent with Raman spectroscopy.展开更多
Aldosterone synthase inhibitors can lessen the production of aldosterone in organisms,which effec-tively affecting the treatment of hypertension.A series of computational approaches like QSAR,docking,DFT and molecular...Aldosterone synthase inhibitors can lessen the production of aldosterone in organisms,which effec-tively affecting the treatment of hypertension.A series of computational approaches like QSAR,docking,DFT and molecular dynamics simulation are applied on 40 benzimidazole derivatives of aldosterone synthase(CYP11B2)in-hibitors.Statistical parameters:Q^(2)=0.877,R^(2)=0.983(CoMFA)and Q^(2)=0.848,R^(2)=0.994(CoMSIA)indicate on good predictive power of both models and DFT’s result illustrates the stability of both models.Besides,Y-randomization test is also performed to ensure the robustness of the obtained 3D-QSAR models.Docking studies show inhibitors rely onπ-πinteraction with residues,such as Phe130,Ala313 and Phe481.Molecular dynamics simulation results further confirm that the hydrophobic interaction with proteins enhances the inhibitor’s inhibitory effect.Based on QSAR studies and molecular docking,we designed novel compounds with enhanced activity against aldosterone synthase.Furthermore,the newly designed compounds are analyzed for their ADMET proper-ties and drug likeness and the results show that they all have excellent bioavailability.展开更多
Molecular dynamics simulation was carried out to study the behavior of liquid 1,2-dichloroethane molecules under external electric fields including direct current field, alternating current field and positive-half-per...Molecular dynamics simulation was carried out to study the behavior of liquid 1,2-dichloroethane molecules under external electric fields including direct current field, alternating current field and positive-half-period cosin field. The maximum applied field strength was 10^8 V/m , the maximum frequency of the alternating current field and that of the positive-half-period cosine field was 10^12 Hz . The simulation revealed that the field type and field strength act on the population of the molecular configuration. In the strong direct current field, all trans forms converted completely into gauche forms. Order parameter and the correlation of the system torsion angle were also investigated. The results suggested that these two dynamical parameters depended also on the field type and the field strength. The maximum of order parameter was found to be at 0.6in the strong direct current field.展开更多
A comparative study of cascades in nanostructured ferritic alloys and pure Fe is performed to reveal the influence of Y_2Ti_2O_7 nanocluster on cascades by molecular dynamics simulations. The cascades with energies of...A comparative study of cascades in nanostructured ferritic alloys and pure Fe is performed to reveal the influence of Y_2Ti_2O_7 nanocluster on cascades by molecular dynamics simulations. The cascades with energies of primary knock-on atom（PKA） ranging from 0.5 keV to 4.0 keV and PKA＇s distances to the interface from 0 to 50 are simulated. It turns out that the Y_2Ti_2O_7 nanocluster can absorb the kinetic energy of cascade atoms, prevent the cascade from extending and reduce the defect production significantly when the cascades overlap with the nanocluster. When the cascade affects seriously the nanocluster, the weak sub-cascade collisions are rebounded by the nanocluster and thus leave more interstitials in the matrix. On the contrary, when the cascade contacts weakly the nanocluster, the interface can pin the arrived interstitials and this leaves more vacancies in the matrix. Moreover, the results indicate that the Y_2Ti_2O_7 nanocluster keeps stable upon the displacement cascade damage.展开更多
The causative pathogen of coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an enveloped virus assembled by a lipid envelope and multiple structural proteins.In this stu...The causative pathogen of coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an enveloped virus assembled by a lipid envelope and multiple structural proteins.In this study,by integrating experimental data,structural modeling,as well as coarse-grained and all-atom molecular dynamics simulations,we constructed multiscale models of SARS-CoV-2.Our 500-ns coarse-grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane-embedded proteins and the surrounding lipid molecules in situ.Our results indicated that the membrane-embedded proteins are highly dynamic,and certain types of lipids exhibit various binding preferences to specific sites of the membrane-embedded proteins.The equilibrated virion model was transformed into atomic resolution,which provided a 3D structure for scientific demonstration and can serve as a framework forfuture exascale allatom molecular dynamics(MD)simulations.A short all-atom molecular dynamics simulation of 255 ps was conducted as a preliminary test for largescale simulationsofthis complexsystem.展开更多
Various types of geofluids exist in deep and ultra-deep layers in petroliferous basins.The geofluids are much more active under high-temperature and high-pressure(HTHP)conditions,but their properties are unclear.We si...Various types of geofluids exist in deep and ultra-deep layers in petroliferous basins.The geofluids are much more active under high-temperature and high-pressure(HTHP)conditions,but their properties are unclear.We simulated the mixing of different fluids in CH_(4)/C_(3)H_(8)/C_(6)H_(14)/C_(8)H_(18)-water systems and C_(6)H_(14)/C_(8)H_(18)-CO_(2)-H_(2)O systems at temperatures of 25℃ to 425℃ and pressures of 5 MPa to 105 MPa,using an in-situ micron quartz capillary tube thermal simulation system and molecular dynamics numerical simulation software.The mixing processes,patterns,and mechanisms of various fluids were analyzed at microscale under increasing temperature and pressure conditions.The results show that the miscibility of fluids in the different alkane-H_(2)O and alkane-CO_(2)-H_(2)O systems is not instantaneous,but the miscibility degree between different fluid phases increases as the temperature and pressure rise during the experiments.The physical thermal experiments(PTEs)show that the mixing process can be divided into three stages:initial miscibility,segmented dynamic miscibility,and complete miscibility.The molecular dynamics numerical simulations(MDNSs)indicate that the mixing process of fluids in the alkane-H_(2)O and alkane CO_(2)-H_(2)O systems can be divided into seven and eight stages,respectively.The carbon number affects the miscibility of alkanes and water,and the temperature and pressure required to reach the same miscibility stage with water increase with the carbon number(C_(3)H_(8),C_(6)H_(14),CH_(4),C_(8)H_(18)).CO_(2) has a critical bridge role in the miscibility of alkanes and water,and its presence significantly reduces the temperatures required to reach the initial,dynamic,and complete miscibility of alkanes and water.The results are of great significance for analyzing and understanding the miscibility of geofluids in deep and ultra-deep HTHP systems.展开更多
CO_(2)injection is an effective enhanced oil recovery technique for energy security with the benefits of carbon neutrality.To reach the maximum oil recovery,the miscible condition between CO_(2)and oil needs to be mai...CO_(2)injection is an effective enhanced oil recovery technique for energy security with the benefits of carbon neutrality.To reach the maximum oil recovery,the miscible condition between CO_(2)and oil needs to be maintained in the reservoir,which requires the operation pressure to be higher than the minimum miscibility pressure(MMP).There are two types of MMPs:the first-contact MMP(FC-MMP)and the multi-contact MMP(MC-MMP).In this study,molecular dynamics simulations were performed for the CO_(2)eoil interface system using two simplified digital oil models:a Bakken dead oil with four lumping components and a live-crude-oil model with 50 types of oil molecules but with no asphaltenes and heavy oil fractions.The vanishing interfacial tension method was used to predict the MMP.Different CO_(2)eoil volume ratios were considered to mimic the different degrees of vaporization.To estimate the MMP accurately and rapidly,the interfacial tension in the low-pressure regime was used for the prediction.Consequently,different MMPs were obtained,where the MMP value increased with increasing CO_(2)eoil volume ratio.FC-MMP can be predicted when the CO_(2)eoil volume ratio is sufficiently high.When the CO_(2)eoil volume ratio was approximately 9e10,MMP was closest to the actual MC-MMP value.The condensing and vaporizing mechanism was also studied at the molecular scale.Because pure CO_(2)was used,only the vaporizing effect on MMP occurred.It was found that the intermediate C2eC6 components have the main effect on the MMP calculation.This study can help to establish a computational protocol to estimate FC-MMP and MC-MMP,which are widely used in reservoir engineering.展开更多
The perfluorosulfonic acid(PFSA) membrane doped with two-dimensional conductive filler Ti_(3)C_(2)T_(x) is a fuel cell proton exchange membrane with high application potential. Experimental studies showed that the pro...The perfluorosulfonic acid(PFSA) membrane doped with two-dimensional conductive filler Ti_(3)C_(2)T_(x) is a fuel cell proton exchange membrane with high application potential. Experimental studies showed that the proton conductivity of Nafion/Ti_(3)C_(2)T_(x) composite membrane is improved significantly compared with that in pure Nafion. However, the microscopic mechanism of doping on the enhancement of membrane performance is remain unclear now. In this work, molecular dynamics simulation was used to investigate the microscopic morphology and proton transport behaviors of Nafion/Ti_(3)C_(2)T_(x) composite membrane at the molecular level. The results shown that there were significant differences about the diffusion kinetics of water molecules and hydroxium ions in Nafion/Ti_(3)C_(2)T_(x) at low and high hydration levels in the nanoscale region.With the increase of water content, Ti_(3)C_(2)T_(x) in membrane was gradually surrounded by ambient water molecules to form a hydration layer, and forming a relatively continuous proton transport channel between Nafion polymer and Ti_(3)C_(2)T_(x) monomer. The continuous proton transport channel could increase the number of binding sites of proton and thus achieving high proton conductivity and high mobility of water molecules at higher hydration level. The current work can provide a theoretical guidance for designing new type of Nafion composite membranes.展开更多
The absorption of CO_(2)is of importance in carbon capture,utilization,and storage technology for greenhouse gas control.In the present work,we clarified the mechanism of how metal-based ionic liquids (MBILs),Bmim[XCl...The absorption of CO_(2)is of importance in carbon capture,utilization,and storage technology for greenhouse gas control.In the present work,we clarified the mechanism of how metal-based ionic liquids (MBILs),Bmim[XCl_(n)]_(m)(X is the metal atom),enhance the CO_(2)absorption capacity of ILs via performing molecular dynamics simulations.The sparse hydrogen bond interaction network constructed by CO_(2)and MBILs was identified through the radial distribution function and interaction energy of CO_(2)-ion pairs,which increase the absorption capacity of CO_(2)in MBILs.Then,the dynamical properties including residence time and self-diffusion coefficient confirmed that MBILs could also promote the diffusion process of CO_(2)in ILs.That's to say,the MBILs can enhance the CO_(2)absorption capacity and the diffusive ability simultaneously.Based on the analysis of structural,energetic and dynamical properties,the CO_(2)absorption capacity of MBILs increases in the order Cl^-→[ZnCl_(4)]^(2-)→[CuCl_(4)]^(2-)→[CrCl_(4)]^-→[FeCl_(4)]^-,revealing the fact that the short metal–Cl bond length and small anion volume could facilitate the performance of CO_(2)absorbing process.These findings show that the metal–Cl bond length and effective volume of the anion can be the effective factors to regulate the CO_(2)absorption process,which can also shed light on the rational molecular design of MBILs for CO_(2)capture and other key chemical engineering processes,such as IL-based gas sensors,nano-electrical devices and so on.展开更多
Long-lasting constant loading commonly exists in silicon-based microelectronic contact,as well as the chemical mechanical polishing area.In this work,the stress relaxation analysis of single crystal silicon coated wit...Long-lasting constant loading commonly exists in silicon-based microelectronic contact,as well as the chemical mechanical polishing area.In this work,the stress relaxation analysis of single crystal silicon coated with an amorphous SiO_(2) film is performed by varying the maximum indentation depth using molecular dynamics simulation.It is found that during holding,the applied indentation force declines sharply at the beginning and then steadily towards the end of the holding period.The stress relaxation amount of bilayer composites increases as the maximum indentation depth increases.It is also found that the deformation features of SiO_(2) film and silicon substrate during holding are inherited from the loading process.The SiO_(2) film during holding is further densified when the maximum indentation depth is equal to or less than a certain value(5.5 nm for the 0.8-nm film).The amount of generated phases and phase distributions of silicon substrate during holding are affected by the plastic deformation of silicon during loading.展开更多
Molecular dynamic simulation is used to study the microstructure of four kinds of ionic liquids(ILs),[Emim]PF6,[Emim][Tf2N],[PC6,6,6,14]PF6 and [PC6,6,6,14][Tf2N] in the capture process of CO2.Radial distribution func...Molecular dynamic simulation is used to study the microstructure of four kinds of ionic liquids(ILs),[Emim]PF6,[Emim][Tf2N],[PC6,6,6,14]PF6 and [PC6,6,6,14][Tf2N] in the capture process of CO2.Radial distribution function(RDF) and spatial distribution function(SDF) are used to analyze the microscopic properties of these systems.The calculated results show that the space distribution of CO2 around ILs determines the capability of ionic liquids for capturing CO2.Based on the analysis of SDF,CO2 and PF6-are overlapped partially around [Emim]+ in [Emim]PF6-CO2 mixture.When the anion is [Tf2N]-,cations are mainly distributed on one side of [Tf2N]-near N atom,and CO2 is concentrated on two sides near the fluoroalkylgroup(?CF3),and there is little overlapped district between cation and CO2.In [PC6,6,6,14]PF6-CO2 mixture,layered structure is found and CO2 is much nearer to PF6-than [PC6,6,6,14]+.Based on the analysis of RDF,in the phosphonium-based ILs,the highest distribution densities of anions and CO2 around cations are about 6 and 3 times as their average ones respectively,while in the imidazolium-based ILs,they are about 3 and 2 respectively,this means that the distributions of CO2 and anions around the imidazolium-based ILs are more evenly distributed than those around the phosphonium-based ILs.展开更多
Integrin activation,the transition from a low to a high affinity state,regulates the numerous cellular responses consequent to integrin engagement by extracellular matrix proteins.Kindlin proteins,play crucial roles i...Integrin activation,the transition from a low to a high affinity state,regulates the numerous cellular responses consequent to integrin engagement by extracellular matrix proteins.Kindlin proteins,play crucial roles in the integrin-signaling pathway by directly interacting with and activating integrins,which mediate the cell-extracellular matrix adhesion and signaling.As a widely distributed PTB domain protein and a major member of the kindlin family,kindlin2 interacts withβ3-tail,bridges talin-activated integrins to promote integrin aggregation,and enhances talin-induced integrin activation.Thus,kindlin2 is identified as a coactivator of integrins.Unlike talins,kindlin2 cannot directly alter the conformation of the integrin transmembrane helix and fail to activate integrin alone.Nevertheless,although it is widely accepted that kindlins and talins synergistically promote integrin activation,the underlying mechanism is unclear.Thus,the study of the force dissociation of the kindlin2/β3-tail complex and the conformation stabilization under different mechanical micro-environments should be of great significance for the further understanding of the structural basis of its synergistically activation of integrin.To reveal the molecular dynamics mechanism of interaction between kindlin2 andβ3-tail,we perform molecular dynamics(MD)simulations for this complex with different computing strategies interaction.In MD simulations,the available crystal structures of Kindlin-2/β3-tail complex(Protein Data Bank code 5XQ1)was downloaded from the PDB database.Two software packages,VMD for visualization and modeling and NAMD 2.13 for energy minimizations and MD simulations,were used here.The steadystate conformation of the complex was obtained from the equilibrium simulation.The dissociation event was observed by the constant velocity simulation,and the mechanical stability of the complex was observed by the constant force simulation.Our results showed that,during the equilibrium of the kindlin2-F3/β34ail complex,the residue MET612,LYS613 and TRP615 on the F3 domain of kindlin2 contributed to hydrogen-bonding with the corresponding residues onβ3 integrin.These bonds exhibit moderate or strong stability through steered molecular dynamics(SMD)simulation.During the constant velocity simulation,the complex exhibits a variety of unfolding pathways against tension applications,which are mainly distinguished by the disruption of hydrogen-bonds between the F3 domain a1/a2 helixes andβ1/β2 sheets.During the constant force simulation,the different phases of the composite force dissociation have different dissociation probabilities,which shows the biphasic force-dependent characteristics.And,the key residues in the pulling were recognized according not only to the number of interacting residue pairs,but also to their bond strength.Using molecular dynamics simulation,we showed the steady state of the kindlin2-F3/β3-tail complex under different tensile forces,and observe the dynamic process of molecular interaction.A possible underlying biophysical mechanism is that,the dissociation of Kindlin2-F3/β3-tail complex is biphasic force-dependent,and the conformations under different stretching states have different binding affinities.This study not only provides insights into the structural basis and mechanical regulation mechanisms of the kindlin/integrin interaction,in understanding in kindlin/integrin-related signaling in different cellular biological processes,but also provides new ideas for novel drug design and the treatment of related diseases.展开更多
Long-lasting constant loading commonly exists in silicon-based microelectronic contact and can lead to the appearance of plastic deformation.Stress relaxation behaviors of monocrystalline silicon coated with amorphous...Long-lasting constant loading commonly exists in silicon-based microelectronic contact and can lead to the appearance of plastic deformation.Stress relaxation behaviors of monocrystalline silicon coated with amorphous SiO_(2)film during nanoindentation are probed using molecular dynamics simulation by varying the indenter’s size.The results show that the indentation force(stress)declines sharply at the initial and decreases almost linearly toward the end of holding for tested samples.The amount of stress relaxation of SiO_(2)/Si samples indented with different indenters during holding increases with growing indenter size,and the corresponding plastic deformation characteristics are carefully analyzed.The deformation mechanism for confined amorphous SiO_(2)film is depicted based on the amorphous plasticity theories,revealing that the more activated shear transformation zones(STZs)and free volume within indented SiO_(2)film promote stress relaxation.The phase transformation takes place to monocrystalline silicon,the generated atoms of Si-II and bct-5 phases within monocrystalline silicon substrate during holding are much higher than those for smaller indenter.展开更多
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Project supported by the National Natural Science Foundation of China(Grant Nos.11705064,11675060,and 91730301)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2662016QD005 and 26622018JC017)the Huazhong Agricultural University Scientific and Technological Self-Innovation Foundation Program,China(Grant No.2015RC021)
文摘Metal ions play critical roles in the interaction between deoxyribonucleic acid(DNA) and protein.The experimental research has demonstrated that the Mg^2+ ion can affect the binding between transcription factor and DNA.In our work,by full-atom molecular dynamic simulation, the effects of the Mg^2+ ion on the cyclic adenosine monophosphate(cAMP)response element binding protein(CREB)/cAMP response elements(CRE) complex are investigated.It is illustrated that the number of hydrogen bonds formed at the interface between protein and DNA is significantly increased when the Mg^2+ ion is added.Hence, an obvious change in the structure of the DNA is observed.Then the DNA base groove and base pair parameters are analyzed.We find that, due to the introduction of the Mg2+ ion, the DNA base major groove becomes narrower.A potential mechanism for this observation is proposed.It is confirmed that the Mg^2+ ion can enhance the stability of the DNA–protein complex.
文摘Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic target for cancer. However, a major problem of current MTHFD2 inhibitors is their lack of selectivity and reactivity with its closest isoform, MTHFD1. Recently, the first selective MTHFD2 inhibitor, DS44960156, has been reported and it exhibits a more than 18-fold selectivity for MTHFD2 over MTHFD1. However, mechanism of DS44960156 selective binding to MTHFD2 over MTHFD1 is unknown. In this study, molecular docking, molecular dynamics (MD) simulations, molecular mechanics generalized born/surface area (MM_GBSA) binding free energy calculations, and analysis of the decomposition of binding free energies were used to investigate the selective binding mechanism of DS44960156 to the folate-binding site of MTHFD2 over MTHFD1. The results revealed that contributions from residues Gln100/Gln132, Val55/Asn87, and Gly237/Gly310 in the binding pocket of MTHFD1/MTHFD2 are the key factors responsible for the binding selectivity. These findings explain the selectivity of DS44960156 to MTHFD2 over MTHFD1, and may provide guidance for the future study and design of novel MTHFD2 inhibitors.
基金Project supported by Shanghai Natural Science Foundation
文摘The investigation results of the bonding structure of CaO-SiO2 slag by means of molecular dynamics simulation are presented. The characteristics of partial radial distribution function gij(r) are in good agreement with the measurement of X-ray diffraction, and the variation of Qn with different SiO4 tetrahedra following the change of Xcao is consistent with the results of Raman spectroscopy, The partial vibrational density of states Fsi(ω) shows that two bands appear in the range of 636-737 cm-1 and 800? 200 cm-1 respectively which are also consistent with Raman spectroscopy.
基金supported by the graduate student innovation project of Chongqing University of Technology (clgycx 20202129)
文摘Aldosterone synthase inhibitors can lessen the production of aldosterone in organisms,which effec-tively affecting the treatment of hypertension.A series of computational approaches like QSAR,docking,DFT and molecular dynamics simulation are applied on 40 benzimidazole derivatives of aldosterone synthase(CYP11B2)in-hibitors.Statistical parameters:Q^(2)=0.877,R^(2)=0.983(CoMFA)and Q^(2)=0.848,R^(2)=0.994(CoMSIA)indicate on good predictive power of both models and DFT’s result illustrates the stability of both models.Besides,Y-randomization test is also performed to ensure the robustness of the obtained 3D-QSAR models.Docking studies show inhibitors rely onπ-πinteraction with residues,such as Phe130,Ala313 and Phe481.Molecular dynamics simulation results further confirm that the hydrophobic interaction with proteins enhances the inhibitor’s inhibitory effect.Based on QSAR studies and molecular docking,we designed novel compounds with enhanced activity against aldosterone synthase.Furthermore,the newly designed compounds are analyzed for their ADMET proper-ties and drug likeness and the results show that they all have excellent bioavailability.
文摘Molecular dynamics simulation was carried out to study the behavior of liquid 1,2-dichloroethane molecules under external electric fields including direct current field, alternating current field and positive-half-period cosin field. The maximum applied field strength was 10^8 V/m , the maximum frequency of the alternating current field and that of the positive-half-period cosine field was 10^12 Hz . The simulation revealed that the field type and field strength act on the population of the molecular configuration. In the strong direct current field, all trans forms converted completely into gauche forms. Order parameter and the correlation of the system torsion angle were also investigated. The results suggested that these two dynamical parameters depended also on the field type and the field strength. The maximum of order parameter was found to be at 0.6in the strong direct current field.
基金Project supported by the Science Challenge Project of China(Grant No.TZ2016002)the National Natural Science Foundation of China(Grant No.50871057)
文摘A comparative study of cascades in nanostructured ferritic alloys and pure Fe is performed to reveal the influence of Y_2Ti_2O_7 nanocluster on cascades by molecular dynamics simulations. The cascades with energies of primary knock-on atom（PKA） ranging from 0.5 keV to 4.0 keV and PKA＇s distances to the interface from 0 to 50 are simulated. It turns out that the Y_2Ti_2O_7 nanocluster can absorb the kinetic energy of cascade atoms, prevent the cascade from extending and reduce the defect production significantly when the cascades overlap with the nanocluster. When the cascade affects seriously the nanocluster, the weak sub-cascade collisions are rebounded by the nanocluster and thus leave more interstitials in the matrix. On the contrary, when the cascade contacts weakly the nanocluster, the interface can pin the arrived interstitials and this leaves more vacancies in the matrix. Moreover, the results indicate that the Y_2Ti_2O_7 nanocluster keeps stable upon the displacement cascade damage.
基金National Key R&D Program of China,Grant/Award Number:2021YFE0108100National Natural Science Foundation of China,Grant Award Numbers:32241031,32171195+1 种基金Tsinghua University Spring Breeze Fund,Grant/Award Number:2021Z99CFZ004Tsinghua University Dushi Fund,Grant/Award Number:2023Z11DSZ001。
文摘The causative pathogen of coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is an enveloped virus assembled by a lipid envelope and multiple structural proteins.In this study,by integrating experimental data,structural modeling,as well as coarse-grained and all-atom molecular dynamics simulations,we constructed multiscale models of SARS-CoV-2.Our 500-ns coarse-grained simulation of the intact virion allowed us to investigate the dynamic behavior of the membrane-embedded proteins and the surrounding lipid molecules in situ.Our results indicated that the membrane-embedded proteins are highly dynamic,and certain types of lipids exhibit various binding preferences to specific sites of the membrane-embedded proteins.The equilibrated virion model was transformed into atomic resolution,which provided a 3D structure for scientific demonstration and can serve as a framework forfuture exascale allatom molecular dynamics(MD)simulations.A short all-atom molecular dynamics simulation of 255 ps was conducted as a preliminary test for largescale simulationsofthis complexsystem.
基金supported by the National Natural Science Foundation of China(Grant Nos.42222208,41821002)the Special Fund for Taishan Scholar Project(Grant No.tsqn201909061)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.20CX06067A)Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(Grant No.2021QNLM020001)。
文摘Various types of geofluids exist in deep and ultra-deep layers in petroliferous basins.The geofluids are much more active under high-temperature and high-pressure(HTHP)conditions,but their properties are unclear.We simulated the mixing of different fluids in CH_(4)/C_(3)H_(8)/C_(6)H_(14)/C_(8)H_(18)-water systems and C_(6)H_(14)/C_(8)H_(18)-CO_(2)-H_(2)O systems at temperatures of 25℃ to 425℃ and pressures of 5 MPa to 105 MPa,using an in-situ micron quartz capillary tube thermal simulation system and molecular dynamics numerical simulation software.The mixing processes,patterns,and mechanisms of various fluids were analyzed at microscale under increasing temperature and pressure conditions.The results show that the miscibility of fluids in the different alkane-H_(2)O and alkane-CO_(2)-H_(2)O systems is not instantaneous,but the miscibility degree between different fluid phases increases as the temperature and pressure rise during the experiments.The physical thermal experiments(PTEs)show that the mixing process can be divided into three stages:initial miscibility,segmented dynamic miscibility,and complete miscibility.The molecular dynamics numerical simulations(MDNSs)indicate that the mixing process of fluids in the alkane-H_(2)O and alkane CO_(2)-H_(2)O systems can be divided into seven and eight stages,respectively.The carbon number affects the miscibility of alkanes and water,and the temperature and pressure required to reach the same miscibility stage with water increase with the carbon number(C_(3)H_(8),C_(6)H_(14),CH_(4),C_(8)H_(18)).CO_(2) has a critical bridge role in the miscibility of alkanes and water,and its presence significantly reduces the temperatures required to reach the initial,dynamic,and complete miscibility of alkanes and water.The results are of great significance for analyzing and understanding the miscibility of geofluids in deep and ultra-deep HTHP systems.
基金financially supported by JX Nippon Oil&Gas Exploration CorporationWe thank the Japan Society for the Promotion of Science(JSPS)for a Grant-in-Aid for Scientific Research A(No.24246148)Grants-in-Aid for Scientific Research C(Nos.16K06925,17K06988,and 22K03927).
文摘CO_(2)injection is an effective enhanced oil recovery technique for energy security with the benefits of carbon neutrality.To reach the maximum oil recovery,the miscible condition between CO_(2)and oil needs to be maintained in the reservoir,which requires the operation pressure to be higher than the minimum miscibility pressure(MMP).There are two types of MMPs:the first-contact MMP(FC-MMP)and the multi-contact MMP(MC-MMP).In this study,molecular dynamics simulations were performed for the CO_(2)eoil interface system using two simplified digital oil models:a Bakken dead oil with four lumping components and a live-crude-oil model with 50 types of oil molecules but with no asphaltenes and heavy oil fractions.The vanishing interfacial tension method was used to predict the MMP.Different CO_(2)eoil volume ratios were considered to mimic the different degrees of vaporization.To estimate the MMP accurately and rapidly,the interfacial tension in the low-pressure regime was used for the prediction.Consequently,different MMPs were obtained,where the MMP value increased with increasing CO_(2)eoil volume ratio.FC-MMP can be predicted when the CO_(2)eoil volume ratio is sufficiently high.When the CO_(2)eoil volume ratio was approximately 9e10,MMP was closest to the actual MC-MMP value.The condensing and vaporizing mechanism was also studied at the molecular scale.Because pure CO_(2)was used,only the vaporizing effect on MMP occurred.It was found that the intermediate C2eC6 components have the main effect on the MMP calculation.This study can help to establish a computational protocol to estimate FC-MMP and MC-MMP,which are widely used in reservoir engineering.
基金financially supported by the National Key R&D Program of China (Nos.2020YFB1505500 and 2020YFB1505503)。
文摘The perfluorosulfonic acid(PFSA) membrane doped with two-dimensional conductive filler Ti_(3)C_(2)T_(x) is a fuel cell proton exchange membrane with high application potential. Experimental studies showed that the proton conductivity of Nafion/Ti_(3)C_(2)T_(x) composite membrane is improved significantly compared with that in pure Nafion. However, the microscopic mechanism of doping on the enhancement of membrane performance is remain unclear now. In this work, molecular dynamics simulation was used to investigate the microscopic morphology and proton transport behaviors of Nafion/Ti_(3)C_(2)T_(x) composite membrane at the molecular level. The results shown that there were significant differences about the diffusion kinetics of water molecules and hydroxium ions in Nafion/Ti_(3)C_(2)T_(x) at low and high hydration levels in the nanoscale region.With the increase of water content, Ti_(3)C_(2)T_(x) in membrane was gradually surrounded by ambient water molecules to form a hydration layer, and forming a relatively continuous proton transport channel between Nafion polymer and Ti_(3)C_(2)T_(x) monomer. The continuous proton transport channel could increase the number of binding sites of proton and thus achieving high proton conductivity and high mobility of water molecules at higher hydration level. The current work can provide a theoretical guidance for designing new type of Nafion composite membranes.
基金financial support of the National Science Foundation of China(No.21808220)。
文摘The absorption of CO_(2)is of importance in carbon capture,utilization,and storage technology for greenhouse gas control.In the present work,we clarified the mechanism of how metal-based ionic liquids (MBILs),Bmim[XCl_(n)]_(m)(X is the metal atom),enhance the CO_(2)absorption capacity of ILs via performing molecular dynamics simulations.The sparse hydrogen bond interaction network constructed by CO_(2)and MBILs was identified through the radial distribution function and interaction energy of CO_(2)-ion pairs,which increase the absorption capacity of CO_(2)in MBILs.Then,the dynamical properties including residence time and self-diffusion coefficient confirmed that MBILs could also promote the diffusion process of CO_(2)in ILs.That's to say,the MBILs can enhance the CO_(2)absorption capacity and the diffusive ability simultaneously.Based on the analysis of structural,energetic and dynamical properties,the CO_(2)absorption capacity of MBILs increases in the order Cl^-→[ZnCl_(4)]^(2-)→[CuCl_(4)]^(2-)→[CrCl_(4)]^-→[FeCl_(4)]^-,revealing the fact that the short metal–Cl bond length and small anion volume could facilitate the performance of CO_(2)absorbing process.These findings show that the metal–Cl bond length and effective volume of the anion can be the effective factors to regulate the CO_(2)absorption process,which can also shed light on the rational molecular design of MBILs for CO_(2)capture and other key chemical engineering processes,such as IL-based gas sensors,nano-electrical devices and so on.
基金The authors thank Zhi Chen for his help in radial distribution function.This study was supported by the National Natural Science Foundation of China(Grant Numbers 51375364,51475359,and 51505479)Natural Science Foundation of Jiangsu Province of China(BK20150184).
文摘Long-lasting constant loading commonly exists in silicon-based microelectronic contact,as well as the chemical mechanical polishing area.In this work,the stress relaxation analysis of single crystal silicon coated with an amorphous SiO_(2) film is performed by varying the maximum indentation depth using molecular dynamics simulation.It is found that during holding,the applied indentation force declines sharply at the beginning and then steadily towards the end of the holding period.The stress relaxation amount of bilayer composites increases as the maximum indentation depth increases.It is also found that the deformation features of SiO_(2) film and silicon substrate during holding are inherited from the loading process.The SiO_(2) film during holding is further densified when the maximum indentation depth is equal to or less than a certain value(5.5 nm for the 0.8-nm film).The amount of generated phases and phase distributions of silicon substrate during holding are affected by the plastic deformation of silicon during loading.
基金Supported by National Basic Research Program of China(No.2009CB219902)National Natural Scientific Fund of China(No.20903098No.20873152)
文摘Molecular dynamic simulation is used to study the microstructure of four kinds of ionic liquids(ILs),[Emim]PF6,[Emim][Tf2N],[PC6,6,6,14]PF6 and [PC6,6,6,14][Tf2N] in the capture process of CO2.Radial distribution function(RDF) and spatial distribution function(SDF) are used to analyze the microscopic properties of these systems.The calculated results show that the space distribution of CO2 around ILs determines the capability of ionic liquids for capturing CO2.Based on the analysis of SDF,CO2 and PF6-are overlapped partially around [Emim]+ in [Emim]PF6-CO2 mixture.When the anion is [Tf2N]-,cations are mainly distributed on one side of [Tf2N]-near N atom,and CO2 is concentrated on two sides near the fluoroalkylgroup(?CF3),and there is little overlapped district between cation and CO2.In [PC6,6,6,14]PF6-CO2 mixture,layered structure is found and CO2 is much nearer to PF6-than [PC6,6,6,14]+.Based on the analysis of RDF,in the phosphonium-based ILs,the highest distribution densities of anions and CO2 around cations are about 6 and 3 times as their average ones respectively,while in the imidazolium-based ILs,they are about 3 and 2 respectively,this means that the distributions of CO2 and anions around the imidazolium-based ILs are more evenly distributed than those around the phosphonium-based ILs.
基金supported by the National Natural Science Foundation of China ( 116272109, 11432006)
文摘Integrin activation,the transition from a low to a high affinity state,regulates the numerous cellular responses consequent to integrin engagement by extracellular matrix proteins.Kindlin proteins,play crucial roles in the integrin-signaling pathway by directly interacting with and activating integrins,which mediate the cell-extracellular matrix adhesion and signaling.As a widely distributed PTB domain protein and a major member of the kindlin family,kindlin2 interacts withβ3-tail,bridges talin-activated integrins to promote integrin aggregation,and enhances talin-induced integrin activation.Thus,kindlin2 is identified as a coactivator of integrins.Unlike talins,kindlin2 cannot directly alter the conformation of the integrin transmembrane helix and fail to activate integrin alone.Nevertheless,although it is widely accepted that kindlins and talins synergistically promote integrin activation,the underlying mechanism is unclear.Thus,the study of the force dissociation of the kindlin2/β3-tail complex and the conformation stabilization under different mechanical micro-environments should be of great significance for the further understanding of the structural basis of its synergistically activation of integrin.To reveal the molecular dynamics mechanism of interaction between kindlin2 andβ3-tail,we perform molecular dynamics(MD)simulations for this complex with different computing strategies interaction.In MD simulations,the available crystal structures of Kindlin-2/β3-tail complex(Protein Data Bank code 5XQ1)was downloaded from the PDB database.Two software packages,VMD for visualization and modeling and NAMD 2.13 for energy minimizations and MD simulations,were used here.The steadystate conformation of the complex was obtained from the equilibrium simulation.The dissociation event was observed by the constant velocity simulation,and the mechanical stability of the complex was observed by the constant force simulation.Our results showed that,during the equilibrium of the kindlin2-F3/β34ail complex,the residue MET612,LYS613 and TRP615 on the F3 domain of kindlin2 contributed to hydrogen-bonding with the corresponding residues onβ3 integrin.These bonds exhibit moderate or strong stability through steered molecular dynamics(SMD)simulation.During the constant velocity simulation,the complex exhibits a variety of unfolding pathways against tension applications,which are mainly distinguished by the disruption of hydrogen-bonds between the F3 domain a1/a2 helixes andβ1/β2 sheets.During the constant force simulation,the different phases of the composite force dissociation have different dissociation probabilities,which shows the biphasic force-dependent characteristics.And,the key residues in the pulling were recognized according not only to the number of interacting residue pairs,but also to their bond strength.Using molecular dynamics simulation,we showed the steady state of the kindlin2-F3/β3-tail complex under different tensile forces,and observe the dynamic process of molecular interaction.A possible underlying biophysical mechanism is that,the dissociation of Kindlin2-F3/β3-tail complex is biphasic force-dependent,and the conformations under different stretching states have different binding affinities.This study not only provides insights into the structural basis and mechanical regulation mechanisms of the kindlin/integrin interaction,in understanding in kindlin/integrin-related signaling in different cellular biological processes,but also provides new ideas for novel drug design and the treatment of related diseases.
基金the National Natural Science Foundation of China(Nos.51375364,51575372)Doctor Funds of Taiyuan University of Science and Technology(No.20202004)。
文摘Long-lasting constant loading commonly exists in silicon-based microelectronic contact and can lead to the appearance of plastic deformation.Stress relaxation behaviors of monocrystalline silicon coated with amorphous SiO_(2)film during nanoindentation are probed using molecular dynamics simulation by varying the indenter’s size.The results show that the indentation force(stress)declines sharply at the initial and decreases almost linearly toward the end of holding for tested samples.The amount of stress relaxation of SiO_(2)/Si samples indented with different indenters during holding increases with growing indenter size,and the corresponding plastic deformation characteristics are carefully analyzed.The deformation mechanism for confined amorphous SiO_(2)film is depicted based on the amorphous plasticity theories,revealing that the more activated shear transformation zones(STZs)and free volume within indented SiO_(2)film promote stress relaxation.The phase transformation takes place to monocrystalline silicon,the generated atoms of Si-II and bct-5 phases within monocrystalline silicon substrate during holding are much higher than those for smaller indenter.
