采用Topomer Co MFA方法对24个二芳基苯胺衍生物进行三维定量构效关系研究,建立了3DQSAR模型,所得优化模型的非交叉相关系数、交互验证系数以及外部验证的复相关系数分别为0.928,0.654和0.940,结果表明该模型具有良好的稳定性和预测能...采用Topomer Co MFA方法对24个二芳基苯胺衍生物进行三维定量构效关系研究,建立了3DQSAR模型,所得优化模型的非交叉相关系数、交互验证系数以及外部验证的复相关系数分别为0.928,0.654和0.940,结果表明该模型具有良好的稳定性和预测能力。采用分子对接技术对药物与受体的作用机制进行了研究,结果显示,药物与HIV-1逆转录酶的LYS172,GLU138,LYS101等位点作用明显。运用这些信息进行分子设计,在理论上获得了一些具有较高活性的新的二芳基苯胺类抗艾滋病药物,该QSAR的研究结果可为新药合成提供理论参考。展开更多
The driven polymer translocation through a nanopore with unbiased initial configuration has been studied by using Langevin dynamics(LD) simulations.It is found that the scaling relationship between translocation time ...The driven polymer translocation through a nanopore with unbiased initial configuration has been studied by using Langevin dynamics(LD) simulations.It is found that the scaling relationship between translocation time and the polymer chain length is strongly affected by the friction coefficient in LD and the driving force.However,there is no scaling relationship between the translocation time and the friction coefficient.The translocation time is almost inversely proportional to the driving force,which is in agreement with those obtained in biased translocation.The scaling relationship between gyration radius(R g) of subchain at the trans side with the subchain length(L) is R g ～L 0.33 that is in good agreement with the limiting value for molten globule state,while the curve of R g of subchain at the cis side has two distinct stages.During translocation,the subchain at the cis side is being stretched gradually,and the structure of the subchain transforms from sphere-like to rod-like.When the effect of stretching reaches the tail end,the subchain is at the most stretched state.Finally the subchain will rapidly restore to coil structure.According to the results of force analysis,the retarding force at the trans side is more crucial during the practical translocation.展开更多
A non-continuous electroosmotic flow model(PFP model)is built based on Poisson equation,Fokker-Planck equation and Navier-Stokse equation,and used to predict the DNA molecule translocation through nanopore.PFP model d...A non-continuous electroosmotic flow model(PFP model)is built based on Poisson equation,Fokker-Planck equation and Navier-Stokse equation,and used to predict the DNA molecule translocation through nanopore.PFP model discards the continuum assumption of ion translocation and considers ions as discrete particles.In addition,this model includes the contributions of Coulomb electrostatic potential between ions,Brownian motion of ions and viscous friction to ion transportation.No ionic diffusion coefficient and other phenomenological parameters are needed in the PFP model.It is worth noting that the PFP model can describe non-equilibrium electroosmotic transportation of ions in a channel of a size comparable with the mean free path of ion.A modified clustering method is proposed for the numerical solution of PFP model,and ion current translocation through nanopore with a radius of 1 nm is simulated using the modified clustering method.The external electric field,wall charge density of nanopore,surface charge density of DNA,as well as ion average number density,influence the electroosmotic velocity profile of electrolyte solution,the velocity of DNA translocation through nanopore and ion current blockade.Results show that the ion average number density of electrolyte and surface charge density of nanopore have a significant effect on the translocation velocity of DNA and the ion current blockade.The translocation velocity of DNA is proportional to the surface charge density of nanopore,and is inversely proportional to ion average number density of electrolyte solution.Thus,the translocation velocity of DNAs can be controlled to improve the accuracy of sequencing by adjusting the external electric field,ion average number density of electrolyte and surface charge density of nanopore.Ion current decreases when the ion average number density is larger than the critical value and increases when the ion average number density is lower than the critical value.Our numerical simulation shows that the translocation velocity of DNA given by the PFP model agrees with the experimental,results better than that given by PNP model or PB model.展开更多
文摘采用Topomer Co MFA方法对24个二芳基苯胺衍生物进行三维定量构效关系研究,建立了3DQSAR模型,所得优化模型的非交叉相关系数、交互验证系数以及外部验证的复相关系数分别为0.928,0.654和0.940,结果表明该模型具有良好的稳定性和预测能力。采用分子对接技术对药物与受体的作用机制进行了研究,结果显示,药物与HIV-1逆转录酶的LYS172,GLU138,LYS101等位点作用明显。运用这些信息进行分子设计,在理论上获得了一些具有较高活性的新的二芳基苯胺类抗艾滋病药物,该QSAR的研究结果可为新药合成提供理论参考。
基金Supported by the National Natural Science Foundation of China (20736002, 20706013)the Open Project of the State Key Laboratory of Chemical Engineering ECUST (SKL-ChE-09C02)the Natural Science Fund of the Education Department of Anhui Province (KJ2011B116)
文摘The driven polymer translocation through a nanopore with unbiased initial configuration has been studied by using Langevin dynamics(LD) simulations.It is found that the scaling relationship between translocation time and the polymer chain length is strongly affected by the friction coefficient in LD and the driving force.However,there is no scaling relationship between the translocation time and the friction coefficient.The translocation time is almost inversely proportional to the driving force,which is in agreement with those obtained in biased translocation.The scaling relationship between gyration radius(R g) of subchain at the trans side with the subchain length(L) is R g ～L 0.33 that is in good agreement with the limiting value for molten globule state,while the curve of R g of subchain at the cis side has two distinct stages.During translocation,the subchain at the cis side is being stretched gradually,and the structure of the subchain transforms from sphere-like to rod-like.When the effect of stretching reaches the tail end,the subchain is at the most stretched state.Finally the subchain will rapidly restore to coil structure.According to the results of force analysis,the retarding force at the trans side is more crucial during the practical translocation.
基金supported by the National Natural Science Foundation(Grant Nos.51375090 and 11172065)
文摘A non-continuous electroosmotic flow model(PFP model)is built based on Poisson equation,Fokker-Planck equation and Navier-Stokse equation,and used to predict the DNA molecule translocation through nanopore.PFP model discards the continuum assumption of ion translocation and considers ions as discrete particles.In addition,this model includes the contributions of Coulomb electrostatic potential between ions,Brownian motion of ions and viscous friction to ion transportation.No ionic diffusion coefficient and other phenomenological parameters are needed in the PFP model.It is worth noting that the PFP model can describe non-equilibrium electroosmotic transportation of ions in a channel of a size comparable with the mean free path of ion.A modified clustering method is proposed for the numerical solution of PFP model,and ion current translocation through nanopore with a radius of 1 nm is simulated using the modified clustering method.The external electric field,wall charge density of nanopore,surface charge density of DNA,as well as ion average number density,influence the electroosmotic velocity profile of electrolyte solution,the velocity of DNA translocation through nanopore and ion current blockade.Results show that the ion average number density of electrolyte and surface charge density of nanopore have a significant effect on the translocation velocity of DNA and the ion current blockade.The translocation velocity of DNA is proportional to the surface charge density of nanopore,and is inversely proportional to ion average number density of electrolyte solution.Thus,the translocation velocity of DNAs can be controlled to improve the accuracy of sequencing by adjusting the external electric field,ion average number density of electrolyte and surface charge density of nanopore.Ion current decreases when the ion average number density is larger than the critical value and increases when the ion average number density is lower than the critical value.Our numerical simulation shows that the translocation velocity of DNA given by the PFP model agrees with the experimental,results better than that given by PNP model or PB model.
