三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。...三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。尽管结构和功能的研究已取得重大进展,但对ABC输出转运体构象门控的分子机制还没有完全理解。由于全原子分子动力学存在长时间尺度问题,因此对ABC蛋白质分子构象变化不能进行完全描述。本文应用粗粒化分子动力学(CG-MD)结合改善的抽样方法,对细菌ABC输出转运体MsbA进行计算模拟研究。本文计算得到的平均力势(potential of mean force,PMF)表明,从OF构象态到IF构象态之间的转变需要经过一个“阻塞态”(occluded state,OC),即MsbA的内门和外门都是关闭的状态。这种阻塞状态对ABC输出功能的方向单一性具有重要意义。我们的CG-MD计算模拟结果显示,随着MsbA的核苷酸结合域(nucleotide binding domain,NBD)的分离,外门的关闭和内门的打开是采用高度协作的方式。基于本文的计算模拟结果,我们提出了一个与目前文献中发表的有很大不同的机械力学模型,揭示了ABC输出转运体通过构象门控运动输运底物的分子机制。展开更多
钾离子通道作为细胞中阳离子浓度的调节器之一,在神经细胞动作电位去极化及复极化过程中起着重要作用.KcsA(K^(+)conduction and selectivity architecture)通道结构简单又具有钾离子通道的共性,常作为钾通道研究的模板.本文采用布朗动...钾离子通道作为细胞中阳离子浓度的调节器之一,在神经细胞动作电位去极化及复极化过程中起着重要作用.KcsA(K^(+)conduction and selectivity architecture)通道结构简单又具有钾离子通道的共性,常作为钾通道研究的模板.本文采用布朗动力学数值方法,系统地对KcsA钾通道的电学特性进行模拟.得到静电场作用下通道内离子的平均势能分布、均匀与非均匀溶液的电流-电压特性曲线、通道轴向的离子浓度分布曲线以及电导-浓度曲线.研究结果发现,KcsA钾离子通道选择性过滤区域几乎完全阻隔了Cl–通过,呈现倾向于K^(+)通过的特异选择特性;其电流-电压曲线基本呈线性分布,电导-浓度曲线呈现先增大后平缓的趋势,基本规律与实验现象一致.另外,还模拟分析了太赫兹场对通道K^(+)电流的影响,相比于仅施加同幅值静电场,选定的0.6 THz,1.2 THz,5 THz的太赫兹场可通过影响离子对之间的相互作用势能,降低通道平均力势,从而增大K^(+)电流.本文的研究不但加深了对于KcsA钾离子通道的规律性认识,还为其他类型离子通道以及太赫兹场对离子通道特性影响的研究提供了新思路.展开更多
We used a combined quantum mechanics and molecular mechanics （QM/MM） method to investigate the solvent effects and potential of mean force of the CH3F＋CN- reaction in water. Comparing to gas phase, the water soluti...We used a combined quantum mechanics and molecular mechanics （QM/MM） method to investigate the solvent effects and potential of mean force of the CH3F＋CN- reaction in water. Comparing to gas phase, the water solution substantially affects the structures of the stationary points along the reaction path. We quantitatively obtained the solvent effects＇ contributions to the reaction： 1.7 kcal/mol to the activation barrier and -26.0 kcal/mol to the reaction free energy. The potential mean of force calculated with the density functional theory/MM theory has a barrier height at 19.7 kcal/mol, consistent with the experimental result at 23.0 kcal/mol; the calculated reaction free energy at -43.5 kcal/mol is also consistent with the one estimated based on the gas-phase data at -39.7 kcal/mol.展开更多
The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitiv...The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitivity to anharmonicity in the hydrogen-nucleus effective potential. The shape of the mean force for amorphous and polycrystalline ice is primarily determined by the anisotropy of the underlying quasi-harmonic effective potential. The data from amorphous ice show an additional curvature reflecting the more pronounced anharmonicity of the effective potential with respect to that of ice Ih.展开更多
A new simulation approach to incorporate hydration force into generalized Langevin dynamics (GLD) is developed in this note. The hydration force determined by the boundary element method (BEM) is taken into account as...A new simulation approach to incorporate hydration force into generalized Langevin dynamics (GLD) is developed in this note. The hydration force determined by the boundary element method (BEM) is taken into account as the mean force terms of solvent including Coulombic interactions with the induced surface charge and the surface pressure of solvent. The exponential model is taken for the friction kernel. A simulation study has been performed on the cyclic undecapeptide cyclosporin A (CPA). The results obtained from the new method (GLDBEM) have been analyzed and compared with that obtained from the molecular dynamics (MD) simulation and the conventional stochastic dynamics (SD) simulation. We have found that the results obtained from GLDBEM show the obvious improvement over the SD simulation technique in the study of molecular structure and dynamic properties.展开更多
The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube （SWCNT） guided by a long SWCNT, either inside or outside the longer tube, is capable of ...The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube （SWCNT） guided by a long SWCNT, either inside or outside the longer tube, is capable of moving along the nanotube axis unidirectionally in an electric field perpendicular to the carbon nanotube （CNT） axis with the linear gradient. The design suggests a new way of molecule transportation or mass delivery. To reveal the mechanism behind this phenomenon, the free energy profiles of the system are calculated by the method of the potential of mean force （PMF）.展开更多
In this work, the traditional method of potential of mean force (PMF) is improved for describing the protein-protein interactions. This method is developed at atomic level and is distance-dependent. Compared with the ...In this work, the traditional method of potential of mean force (PMF) is improved for describing the protein-protein interactions. This method is developed at atomic level and is distance-dependent. Compared with the traditional method, our model can reasonably consider the effects of the environ- mental factors. With this modification, we can obtain more reasonable and accurate pair potentials, which are the pre-requisite for precisely describing the protein-protein interactions and can help us to recognize the interaction rules of residues in protein systems. Our method can also be applied to other fields of protein science, e.g., protein fold recognition, structure prediction and prediction of thermo- stability.展开更多
基金supported by the National Natural Science Foundation of China(21073170,21273209).
文摘三磷酸腺苷结合盒式(ATP-binding cassette,ABC)输出转运体是一类典型的蛋白质分子机器,这类分子机器通过门控运动进行“向外打开”(outward-facing,OF)和“向内打开”(inward-facing,IF)构象态之间转换,从而把底物转运输出生物膜外。尽管结构和功能的研究已取得重大进展,但对ABC输出转运体构象门控的分子机制还没有完全理解。由于全原子分子动力学存在长时间尺度问题,因此对ABC蛋白质分子构象变化不能进行完全描述。本文应用粗粒化分子动力学(CG-MD)结合改善的抽样方法,对细菌ABC输出转运体MsbA进行计算模拟研究。本文计算得到的平均力势(potential of mean force,PMF)表明,从OF构象态到IF构象态之间的转变需要经过一个“阻塞态”(occluded state,OC),即MsbA的内门和外门都是关闭的状态。这种阻塞状态对ABC输出功能的方向单一性具有重要意义。我们的CG-MD计算模拟结果显示,随着MsbA的核苷酸结合域(nucleotide binding domain,NBD)的分离,外门的关闭和内门的打开是采用高度协作的方式。基于本文的计算模拟结果,我们提出了一个与目前文献中发表的有很大不同的机械力学模型,揭示了ABC输出转运体通过构象门控运动输运底物的分子机制。
基金Project supported by the National Natural Science Foundation of China(Grant No.11774206)Taishan Scholarship Fund from Shandong Province,China
文摘We used a combined quantum mechanics and molecular mechanics （QM/MM） method to investigate the solvent effects and potential of mean force of the CH3F＋CN- reaction in water. Comparing to gas phase, the water solution substantially affects the structures of the stationary points along the reaction path. We quantitatively obtained the solvent effects＇ contributions to the reaction： 1.7 kcal/mol to the activation barrier and -26.0 kcal/mol to the reaction free energy. The potential mean of force calculated with the density functional theory/MM theory has a barrier height at 19.7 kcal/mol, consistent with the experimental result at 23.0 kcal/mol; the calculated reaction free energy at -43.5 kcal/mol is also consistent with the one estimated based on the gas-phase data at -39.7 kcal/mol.
文摘The hydrogen mean force from experimental neutron Compton profiles is derived using deep inelastic neutron scattering on amorphous and polycrystalline ice. The formalism of mean force is extended to probe its sensitivity to anharmonicity in the hydrogen-nucleus effective potential. The shape of the mean force for amorphous and polycrystalline ice is primarily determined by the anisotropy of the underlying quasi-harmonic effective potential. The data from amorphous ice show an additional curvature reflecting the more pronounced anharmonicity of the effective potential with respect to that of ice Ih.
基金Supported by National Natural Science Foundation of China(No.51674234,21606232,91434203,21506014)Natural Science Foundation of Liaoning Province of China(No.201602003)Educational Commission of Liaoning Province of China(No.2016006)
基金supported by the National Natural Science Foundation of China(11405113)Science and Technology Plan of Sichuan Province+2 种基金China(2010JY0122)Science Research Fund of Sichuan Normal UniversityChina(10MSL02)
文摘A new simulation approach to incorporate hydration force into generalized Langevin dynamics (GLD) is developed in this note. The hydration force determined by the boundary element method (BEM) is taken into account as the mean force terms of solvent including Coulombic interactions with the induced surface charge and the surface pressure of solvent. The exponential model is taken for the friction kernel. A simulation study has been performed on the cyclic undecapeptide cyclosporin A (CPA). The results obtained from the new method (GLDBEM) have been analyzed and compared with that obtained from the molecular dynamics (MD) simulation and the conventional stochastic dynamics (SD) simulation. We have found that the results obtained from GLDBEM show the obvious improvement over the SD simulation technique in the study of molecular structure and dynamic properties.
基金Project supported by the National Natural Science Foundation of China(Nos.11372175 and 11272197)the Research Fund for the Doctoral Program of Higher Education of China(No.20103108110004)the Innovation Program of Shanghai Municipality Education Commission(No.14ZZ095)
文摘The molecular dynamics simulations are performed to show that in aque- ous environments, a short single-walled carbon nanotube （SWCNT） guided by a long SWCNT, either inside or outside the longer tube, is capable of moving along the nanotube axis unidirectionally in an electric field perpendicular to the carbon nanotube （CNT） axis with the linear gradient. The design suggests a new way of molecule transportation or mass delivery. To reveal the mechanism behind this phenomenon, the free energy profiles of the system are calculated by the method of the potential of mean force （PMF）.
基金the National Natural Science Foundation of China (Grant Nos. 90403120, 10474041 and 10504012)
文摘In this work, the traditional method of potential of mean force (PMF) is improved for describing the protein-protein interactions. This method is developed at atomic level and is distance-dependent. Compared with the traditional method, our model can reasonably consider the effects of the environ- mental factors. With this modification, we can obtain more reasonable and accurate pair potentials, which are the pre-requisite for precisely describing the protein-protein interactions and can help us to recognize the interaction rules of residues in protein systems. Our method can also be applied to other fields of protein science, e.g., protein fold recognition, structure prediction and prediction of thermo- stability.
