Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple...Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic （MD） simulation for model 0020 was conducted in normal saline （0.9%, w/F） under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers （ARBs）. The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-n interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design：展开更多
An element-free Galerkin method(EFGM) is used to solve the two-dimensional(2D) ground penetrating radar(GPR)modelling problems, due to its simple pre-processing, the absence of elements and high accuracy. Different fr...An element-free Galerkin method(EFGM) is used to solve the two-dimensional(2D) ground penetrating radar(GPR)modelling problems, due to its simple pre-processing, the absence of elements and high accuracy. Different from element-based numerical methods, this approach makes nodes free from the elemental restraint and avoids the explicit mesh discretization. First, we derived the boundary value problem for the 2D GPR simulation problems. Second, a penalty function approach and a boundary condition truncated method were used to enforce the essential and the absorbing boundary conditions, respectively. A three-layered GPR model was used to verify our element-free approach. The numerical solutions show that our solutions have an excellent agreement with solutions of a finite element method(FEM). Then, we used the EFGM to simulate one more complex model to show its capability and limitations. Simulation results show that one obvious advantage of EFGM is the absence of element mesh, which makes the method very flexible. Due to the use of MLS fitting, a key feature of EFM, is that both the dependent variable and its gradient are continuous and have high precision.展开更多
基金Project(20876180)supported by the National Natural Science Foundation of China
文摘Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic （MD） simulation for model 0020 was conducted in normal saline （0.9%, w/F） under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers （ARBs）. The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-n interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design：
基金Project(41074085)supported by the National Natural Science Foundation of ChinaProject(NCET-12-0551)supported by the Funds for New Century Excellent Talents in University,ChinaProject supported by Shenghua Yuying Program of Central South University,China
文摘An element-free Galerkin method(EFGM) is used to solve the two-dimensional(2D) ground penetrating radar(GPR)modelling problems, due to its simple pre-processing, the absence of elements and high accuracy. Different from element-based numerical methods, this approach makes nodes free from the elemental restraint and avoids the explicit mesh discretization. First, we derived the boundary value problem for the 2D GPR simulation problems. Second, a penalty function approach and a boundary condition truncated method were used to enforce the essential and the absorbing boundary conditions, respectively. A three-layered GPR model was used to verify our element-free approach. The numerical solutions show that our solutions have an excellent agreement with solutions of a finite element method(FEM). Then, we used the EFGM to simulate one more complex model to show its capability and limitations. Simulation results show that one obvious advantage of EFGM is the absence of element mesh, which makes the method very flexible. Due to the use of MLS fitting, a key feature of EFM, is that both the dependent variable and its gradient are continuous and have high precision.
