In this paper,a new kind of flexible cone composed of the thin-walled plates based on space probecone docking mechanism for small-sized spacecraft is presented.The theoretical model of docking impact dynamics,which ta...In this paper,a new kind of flexible cone composed of the thin-walled plates based on space probecone docking mechanism for small-sized spacecraft is presented.The theoretical model of docking impact dynamics,which takes into account the additional stiffness terms,is derived based on Lagrange Analytical Mechanics theory and Hertz contact theory.Finite element method is employed for the discretization of the thin-walled plate.The results show that the traditional dynamic model without considering the additional stiffness terms will be difficult to reach steady state.The method proposed in this paper can correctly predict the dynamic behavior of the system.展开更多
BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug des...BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.展开更多
Recent developments in micro- and nano-satellites have attracted the interest of the research community worldwide. Many colleges and corporations have launched their satellites in space. Meanwhile, the space flexible ...Recent developments in micro- and nano-satellites have attracted the interest of the research community worldwide. Many colleges and corporations have launched their satellites in space. Meanwhile, the space flexible probe-cone docking system for micro- and nano-satellites has become an attractive topic. In this paper, a dynamic model of a space flexible probe-cone dock- ing system, in which the flexible beam technology is applied, is built based on the Kane method. The curves of impact force versus time are obtained by the Lagrange model, the Kane model, and the experimental method. The Lagrange model was presented in the reference and verified by both finite element simulation and experiment. The results of the three methods show good agreements on the condition that the beam flexibility and the initial relative velocity change. It is worth mentioning that the introduction of vectorial mechanics and analytical mechanics in the Kane method leads to a large reduction of differential operations and makes the modeling process much easier than that of the Lagrange method. Moreover, the influences of the beam flexibility and the initial relative velocity are discussed. It is concluded that the initial relative velocity of space docking operation should be controlled to a certain value in order to protect the docking system.展开更多
To make further studies on the difference of cis-nitenpyram analogues, a series of cis-nitenpyram com- pounds containing a flexible amido segment anchored on tetrahydropyrimidine ring was designed and synthesized. Pre...To make further studies on the difference of cis-nitenpyram analogues, a series of cis-nitenpyram com- pounds containing a flexible amido segment anchored on tetrahydropyrimidine ring was designed and synthesized. Preliminary bioassays indicate that all the analogues exhibit a mortality of 100% at 100 rag/L, and the analogue 4d shows the best activity against Nilaparvata lugens and Myzus persicae, with a mortality of 100% at 4 mg/L （LCs0=0.172 rag/L）. The structure activity relationship studies show that insecticidal activities of the analogues are affected by the kinds and size of substituent R. In addition, the molecular docking simulations reveal that compouds 4 with a flexible amido segment on tetrahydropyrimidine ring show their different binding affinities for the nicotinic acetyleholine receptor（nAChR） of insect and compoud 4d shows stronger hydrogen-bonding with nAChR, which may provide the structure-activity relationship observed in vitro.展开更多
Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interac- tion and surface h...Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interac- tion and surface hydrophobic effect of proteins, hence quantitatively giving rise to a binary linear rela- tion between HIC retention time (RT) at concentrated salting liquid and ligand-protein binding free en- ergy. Then, possible binding manners for 27 proteins of known crystal structures with hydrophobic ligands are simulated and analyzed via ICM flexible molecular docking and genetic algorithm, with re- sults greatly consistent with experimental values. By investigation, it is confirmed local hydrophobic effects of proteins and nonbinding/conformation interaction between ligand and protein both notably influence HIC chromatogram retention behaviors, mainly focusing on exposed portions on the protein surface.展开更多
基金Supported by the National Natural Science Foundation of China(91216201,11725211)
文摘In this paper,a new kind of flexible cone composed of the thin-walled plates based on space probecone docking mechanism for small-sized spacecraft is presented.The theoretical model of docking impact dynamics,which takes into account the additional stiffness terms,is derived based on Lagrange Analytical Mechanics theory and Hertz contact theory.Finite element method is employed for the discretization of the thin-walled plate.The results show that the traditional dynamic model without considering the additional stiffness terms will be difficult to reach steady state.The method proposed in this paper can correctly predict the dynamic behavior of the system.
基金supported by the National Natural Science Foundation of China(21102181,81302634 and 21572273)
文摘BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.
基金supported in part by the National Natural Science Foundation of China (Nos. 91216201, 51205403)
文摘Recent developments in micro- and nano-satellites have attracted the interest of the research community worldwide. Many colleges and corporations have launched their satellites in space. Meanwhile, the space flexible probe-cone docking system for micro- and nano-satellites has become an attractive topic. In this paper, a dynamic model of a space flexible probe-cone dock- ing system, in which the flexible beam technology is applied, is built based on the Kane method. The curves of impact force versus time are obtained by the Lagrange model, the Kane model, and the experimental method. The Lagrange model was presented in the reference and verified by both finite element simulation and experiment. The results of the three methods show good agreements on the condition that the beam flexibility and the initial relative velocity change. It is worth mentioning that the introduction of vectorial mechanics and analytical mechanics in the Kane method leads to a large reduction of differential operations and makes the modeling process much easier than that of the Lagrange method. Moreover, the influences of the beam flexibility and the initial relative velocity are discussed. It is concluded that the initial relative velocity of space docking operation should be controlled to a certain value in order to protect the docking system.
文摘To make further studies on the difference of cis-nitenpyram analogues, a series of cis-nitenpyram com- pounds containing a flexible amido segment anchored on tetrahydropyrimidine ring was designed and synthesized. Preliminary bioassays indicate that all the analogues exhibit a mortality of 100% at 100 rag/L, and the analogue 4d shows the best activity against Nilaparvata lugens and Myzus persicae, with a mortality of 100% at 4 mg/L （LCs0=0.172 rag/L）. The structure activity relationship studies show that insecticidal activities of the analogues are affected by the kinds and size of substituent R. In addition, the molecular docking simulations reveal that compouds 4 with a flexible amido segment on tetrahydropyrimidine ring show their different binding affinities for the nicotinic acetyleholine receptor（nAChR） of insect and compoud 4d shows stronger hydrogen-bonding with nAChR, which may provide the structure-activity relationship observed in vitro.
基金Supported by National Project 863 Fund (Grant No. 2006AA02Z312)State Key Laboratory of Chemo Biosensing and Chemometrics Foundation (Grant No. 0501201)
文摘Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interac- tion and surface hydrophobic effect of proteins, hence quantitatively giving rise to a binary linear rela- tion between HIC retention time (RT) at concentrated salting liquid and ligand-protein binding free en- ergy. Then, possible binding manners for 27 proteins of known crystal structures with hydrophobic ligands are simulated and analyzed via ICM flexible molecular docking and genetic algorithm, with re- sults greatly consistent with experimental values. By investigation, it is confirmed local hydrophobic effects of proteins and nonbinding/conformation interaction between ligand and protein both notably influence HIC chromatogram retention behaviors, mainly focusing on exposed portions on the protein surface.
