We report the results of protein folding （219M, C34, N36, 2KES, 2KHK） by the method of accelerated molecular dynamics （aMD） at room temperature with the implicit solvent model. Starting from the linear structures,...We report the results of protein folding （219M, C34, N36, 2KES, 2KHK） by the method of accelerated molecular dynamics （aMD） at room temperature with the implicit solvent model. Starting from the linear structures, these proteins successfully fold to the native structure in a lO0-ns aMD simulation. In contrast, they are failed under the traditional MD simulation in the same simulation time. Then we find that the lowest root mean square deviations of helix structures from the native structures are 0.36 A, 0.63 A, 0.52 A, 1.1 A and 0.78 A. What is more, native contacts, cluster and free energy analyses show that the results of the aMD method are in accordance with the experiment very well. All analyses show that the aMD can accelerate the simulation process, thus we may apply it to the field of computer aided drug designs.展开更多
One major cause of Alzheimer’s disease(AD) is evidently due to the aggregation and deposition of amyloidβ peptides(Aβ) in the brain tissue of the patient. Preventing misfolding and self-aggregation of Aβ protein c...One major cause of Alzheimer’s disease(AD) is evidently due to the aggregation and deposition of amyloidβ peptides(Aβ) in the brain tissue of the patient. Preventing misfolding and self-aggregation of Aβ protein can reduce the formation of highly toxic polymer, which is important for the treatment of AD. Among them, the α-helix consisting of42 residues(Aβ42) is the main component of senile plaques in AD. In this paper, 500 ns accelerated molecular dynamics are performed at different temperatures(300 K, 350 K, 400 K, 450 K) to study of the effect of temperature-induced conformation changes of Aβ42 protein during the unfolding process respectively.展开更多
The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the ...The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.展开更多
In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. The...In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. Then a parallel molecular dynamics（MD） simulation is employed to equilibrate the Cl C-ec1 structure for 27.5 ns at temperature 298.15 K. Based on this equilibrated structure,we compute the channel geometric size variation and electrostatic potential distribution along the channel. Meanwhile,Cl^- transport process is simulated using oriented random walk method under variable external potential. The simulation result shows that Cl^- transport velocity depends on the width of the narrowest channel region. Mutation of negative glutamate E148 can produce positive potential,which is beneficial for Cl^- transport,around external Cl^- binding region in the channel. The simulated current-voltage curves about Cl^- transporting in Cl C-ec1 protein agree with Jayaram＇s experimental results.展开更多
We introduce a non-uniform gravity-like force field to control the granular flow state in a quasi-one- dimensional system, and study the system by the molecular dynamics simulation. We find that the granular flow unde...We introduce a non-uniform gravity-like force field to control the granular flow state in a quasi-one- dimensional system, and study the system by the molecular dynamics simulation. We find that the granular flow under non-uniform force field can be well described by a density wave with fixed time period if a fixed partiele number condition is used. The base frequency of the density wave does not depend on the position of the flow, while both the average density and oseillation amplitude of the flow vary continuously with the position. The formation of the density wave results from the aggregation of the granules in the decelerated region and the feed-back mechanism in the fixed particle number condition.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos 31200545,11274206 and 11574184
文摘We report the results of protein folding （219M, C34, N36, 2KES, 2KHK） by the method of accelerated molecular dynamics （aMD） at room temperature with the implicit solvent model. Starting from the linear structures, these proteins successfully fold to the native structure in a lO0-ns aMD simulation. In contrast, they are failed under the traditional MD simulation in the same simulation time. Then we find that the lowest root mean square deviations of helix structures from the native structures are 0.36 A, 0.63 A, 0.52 A, 1.1 A and 0.78 A. What is more, native contacts, cluster and free energy analyses show that the results of the aMD method are in accordance with the experiment very well. All analyses show that the aMD can accelerate the simulation process, thus we may apply it to the field of computer aided drug designs.
基金Supported by the National Natural Science Foundation of China under Grant Nos.11574184,11774207the Natural Science Foundation of Shandong Province under Grant No.ZR2016JL003Primary Research&Development Plan of Shandong Province under Grant No.2017GSF18108
文摘One major cause of Alzheimer’s disease(AD) is evidently due to the aggregation and deposition of amyloidβ peptides(Aβ) in the brain tissue of the patient. Preventing misfolding and self-aggregation of Aβ protein can reduce the formation of highly toxic polymer, which is important for the treatment of AD. Among them, the α-helix consisting of42 residues(Aβ42) is the main component of senile plaques in AD. In this paper, 500 ns accelerated molecular dynamics are performed at different temperatures(300 K, 350 K, 400 K, 450 K) to study of the effect of temperature-induced conformation changes of Aβ42 protein during the unfolding process respectively.
基金financially supported by the Science and Technology Development Fund(FDCT)of Macao(0029/2018/A1,China)the University of Macao Research Grants(MYRG2019-00041-ICMS,China)performed in part at the High-Performance Computing Cluster(HPCC)which is supported by Information and Communication Technology Office(ICTO)of the University of Macao,China。
文摘The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and money-consuming.This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods.Random forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation.The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of oil-surfactant-cosurfactant.Finally,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of cosurfactants.In conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation design.The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.
基金Supported by the National Natural Science Foundation of China(11304123)the Scientific Research Foundation of Jianghan University(2013016)
文摘In order to illustrate the ion transport mechanism of chloride channel（Cl C） protein,a type of Cl C protein,Cl C-ec1,from Escherichia coli is embedded into an explicit membranewater system by using software VMD. Then a parallel molecular dynamics（MD） simulation is employed to equilibrate the Cl C-ec1 structure for 27.5 ns at temperature 298.15 K. Based on this equilibrated structure,we compute the channel geometric size variation and electrostatic potential distribution along the channel. Meanwhile,Cl^- transport process is simulated using oriented random walk method under variable external potential. The simulation result shows that Cl^- transport velocity depends on the width of the narrowest channel region. Mutation of negative glutamate E148 can produce positive potential,which is beneficial for Cl^- transport,around external Cl^- binding region in the channel. The simulated current-voltage curves about Cl^- transporting in Cl C-ec1 protein agree with Jayaram＇s experimental results.
基金Supported by the National Basic Research Program of China under Grant No.2009CB930800by the National Natural Science Foundation of China under Grant Nos.10875166 and 11274355
文摘We introduce a non-uniform gravity-like force field to control the granular flow state in a quasi-one- dimensional system, and study the system by the molecular dynamics simulation. We find that the granular flow under non-uniform force field can be well described by a density wave with fixed time period if a fixed partiele number condition is used. The base frequency of the density wave does not depend on the position of the flow, while both the average density and oseillation amplitude of the flow vary continuously with the position. The formation of the density wave results from the aggregation of the granules in the decelerated region and the feed-back mechanism in the fixed particle number condition.
