A model of crosslinker unbinding is implemented in a highly coarse- grained granular model of F-actin cytoskeleton. We employ this specific granular model to study the mechanisms of the compressive responses of F-acti...A model of crosslinker unbinding is implemented in a highly coarse- grained granular model of F-actin cytoskeleton. We employ this specific granular model to study the mechanisms of the compressive responses of F-actin networks. It is found that the compressive response of F-actin cytoskeleton has dependency on the strain rate. The evolution of deformation energy in the network indicates that crosslinker unbinding events can induce the remodelling of F-actin cytoskele- ton in response to external loadings. The internal stress in F-actin cytoskeleton can efficiently dissipate with the help of crosslinker unbinding, which could lead to the soontaneous relaxation of living cells.展开更多
Mechanical force plays a critical role in the remodeling and degradation of cartilage tissues.The cartilage tissue generates,absorbs,and transmits mechanical force,enabling specific biological processes in our body.A ...Mechanical force plays a critical role in the remodeling and degradation of cartilage tissues.The cartilage tissue generates,absorbs,and transmits mechanical force,enabling specific biological processes in our body.A moderate intensity mechanical force is necessary for cartilage tissue remodeling and the adaptation of biomechanical properties,but a high intensity mechanical force can lead to pathological degradation of cartilage tissue.However,the molecular mechanism of cartilage degradation is still unclear.We use full atomistic simulations with SMD simulations to investigate whether the magnitude of mechanical force affects the unbinding pathway of the MMP8-Aggrecan_IGD complex.We find that when the pulling velocity is slow,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is higher,and a three-step unbinding pathway is observed.On the other hand,when the pulling velocity is fast,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is lower,and a two-step unbinding pathway is observed.Our results help us to understand how the magnitude of the mechanical force affects the unbinding pathway of the enzyme-ligand complex in cartilage tissue at the molecular level.展开更多
Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM d...Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.展开更多
We study an exclusion process with multiple dynamic roadblocks.Each roadblock can move diffusively forward or backward with different rates,as well as unbind from/rebind to a free site.By Monte Carlo simulations,the t...We study an exclusion process with multiple dynamic roadblocks.Each roadblock can move diffusively forward or backward with different rates,as well as unbind from/rebind to a free site.By Monte Carlo simulations,the two moving types are investigated in combination of roadblock number.The case of only diffusive roadblocks shows an asymmetric current-density relation.The case of only long-range jumping roadblocks presents that flux decreases with increasing roadblock number.展开更多
Ions in the bulk of solvent-free ionic liquids bind into ion pairs and clusters.The competition between the propensity of ions to stay in a bound state,and the reduction of the energy when unbinding in electric field,...Ions in the bulk of solvent-free ionic liquids bind into ion pairs and clusters.The competition between the propensity of ions to stay in a bound state,and the reduction of the energy when unbinding in electric field,determines the portion of free ions in the electrical double layer.We present the simplest possible mean-field theory to study this effect."Cracking"of ion pairs into free ions in electric field is accompanied by the change of the dielectric response of the ionic liquid.The predictions from the theory are verified and further explored by molecular dynamics simulations.A particular finding of the theory is that the differential capacitance vs potential curve displays a bell shape,despite the low concentration of free charge carriers,because the dielectric response reduces the threshold concentration for the bell-to camelshape transition.The presented theory does not take into account overscreening and oscillating charge distributions in the electrical double layer.But in spite of the simplicity of the model,its findings demonstrate a clear physical effect:a preference to be a charged monopole rather than a dipole(or higher order multipole)in strong electric field.展开更多
Since 1949,Chinese mainland historians and creators in film and television,novels,and reportage have continued to shape the heroic image of female groups in the base areas of the Communist Party of China(CPC)during th...Since 1949,Chinese mainland historians and creators in film and television,novels,and reportage have continued to shape the heroic image of female groups in the base areas of the Communist Party of China(CPC)during the Anti-Japanese War.They participated in production,women's mobilization,and reconstruction of the rural political order Tike men.55 They pursued the equality between men and women,marked by freedom of marriage,and also participated in regional guerrilla warfare to combat the Japanese puppet army"as men."However,in the remote villages of north China at the end of the Qing dynasty and the beginning of the Republic of China,it was not common for women to unbind their feet.In wartime,most women over twenty years of age were forever left with the"three-inch golden lotus"(sancun jinlian)feet.The damage of the war accelerated their acceptance of the CPC's emancipation concepts and policies and presented them with an opportunity to actively implement them.The experience of survival drastically changed traditional aesthetics,ideas,and customs related to women.Physical and psychological changes occurred as a result of the war;women began to go out of their homes to participate in the work of the Women's Salvation Association and the Youth Salvation Association,and a group of women achieved marriage equality between men and women in the form of"divorce her husband"(qi xiu fu).Due to pressure,women carried more physical and mental responsibilities,faced insufficient advocacy for their rights,and the aesthetics and mentality of womanhood underwent change.展开更多
基金supported by the ARC Future Fellowship Grant(FT100100172)
文摘A model of crosslinker unbinding is implemented in a highly coarse- grained granular model of F-actin cytoskeleton. We employ this specific granular model to study the mechanisms of the compressive responses of F-actin networks. It is found that the compressive response of F-actin cytoskeleton has dependency on the strain rate. The evolution of deformation energy in the network indicates that crosslinker unbinding events can induce the remodelling of F-actin cytoskele- ton in response to external loadings. The internal stress in F-actin cytoskeleton can efficiently dissipate with the help of crosslinker unbinding, which could lead to the soontaneous relaxation of living cells.
文摘Mechanical force plays a critical role in the remodeling and degradation of cartilage tissues.The cartilage tissue generates,absorbs,and transmits mechanical force,enabling specific biological processes in our body.A moderate intensity mechanical force is necessary for cartilage tissue remodeling and the adaptation of biomechanical properties,but a high intensity mechanical force can lead to pathological degradation of cartilage tissue.However,the molecular mechanism of cartilage degradation is still unclear.We use full atomistic simulations with SMD simulations to investigate whether the magnitude of mechanical force affects the unbinding pathway of the MMP8-Aggrecan_IGD complex.We find that when the pulling velocity is slow,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is higher,and a three-step unbinding pathway is observed.On the other hand,when the pulling velocity is fast,the mechanical force required to unbind the Aggrecan_IGD from MMP8 is lower,and a two-step unbinding pathway is observed.Our results help us to understand how the magnitude of the mechanical force affects the unbinding pathway of the enzyme-ligand complex in cartilage tissue at the molecular level.
基金National Natural Science Foundation of China(22073030)the Oriental Scholars of Shanghai Universities。
文摘Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.
基金Project supported by the National Basic Research Program of China(Grant No.2012CB725404)the National Natural Science Foundation of China(Grant Nos.11422221,71171185,and 71371175)
文摘We study an exclusion process with multiple dynamic roadblocks.Each roadblock can move diffusively forward or backward with different rates,as well as unbind from/rebind to a free site.By Monte Carlo simulations,the two moving types are investigated in combination of roadblock number.The case of only diffusive roadblocks shows an asymmetric current-density relation.The case of only long-range jumping roadblocks presents that flux decreases with increasing roadblock number.
基金funding support from the National Natural Science Foundation of China(51876072)financial support from National Natural Science Foundation of China(21802170)+2 种基金supported through a studentship of the Centre for Doctoral Training on Theory and Simulation of Materials at Imperial College London,funded by the EPSRC(EP/L015579/1)the funding from the Thomas Young Centre under grant number TYC-101funding from the Leverhulme Trust(Grant No.RPG2016-223)
文摘Ions in the bulk of solvent-free ionic liquids bind into ion pairs and clusters.The competition between the propensity of ions to stay in a bound state,and the reduction of the energy when unbinding in electric field,determines the portion of free ions in the electrical double layer.We present the simplest possible mean-field theory to study this effect."Cracking"of ion pairs into free ions in electric field is accompanied by the change of the dielectric response of the ionic liquid.The predictions from the theory are verified and further explored by molecular dynamics simulations.A particular finding of the theory is that the differential capacitance vs potential curve displays a bell shape,despite the low concentration of free charge carriers,because the dielectric response reduces the threshold concentration for the bell-to camelshape transition.The presented theory does not take into account overscreening and oscillating charge distributions in the electrical double layer.But in spite of the simplicity of the model,its findings demonstrate a clear physical effect:a preference to be a charged monopole rather than a dipole(or higher order multipole)in strong electric field.
文摘Since 1949,Chinese mainland historians and creators in film and television,novels,and reportage have continued to shape the heroic image of female groups in the base areas of the Communist Party of China(CPC)during the Anti-Japanese War.They participated in production,women's mobilization,and reconstruction of the rural political order Tike men.55 They pursued the equality between men and women,marked by freedom of marriage,and also participated in regional guerrilla warfare to combat the Japanese puppet army"as men."However,in the remote villages of north China at the end of the Qing dynasty and the beginning of the Republic of China,it was not common for women to unbind their feet.In wartime,most women over twenty years of age were forever left with the"three-inch golden lotus"(sancun jinlian)feet.The damage of the war accelerated their acceptance of the CPC's emancipation concepts and policies and presented them with an opportunity to actively implement them.The experience of survival drastically changed traditional aesthetics,ideas,and customs related to women.Physical and psychological changes occurred as a result of the war;women began to go out of their homes to participate in the work of the Women's Salvation Association and the Youth Salvation Association,and a group of women achieved marriage equality between men and women in the form of"divorce her husband"(qi xiu fu).Due to pressure,women carried more physical and mental responsibilities,faced insufficient advocacy for their rights,and the aesthetics and mentality of womanhood underwent change.
