The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on th...The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on the basis of shadow projections. This article provides basic information regarding CAD of X-ray microtomography and a scheme consisting of three levels. The article also shows basic relations of X-ray computed tomography, the generalized scheme of an X-ray microtomographic scanner. The methods of X-ray imaging of the spatial microstructure and morphometry of materials are described. The main characteristics of an X-ray microtomographic scanner, the X-ray source, X-ray optical elements and mechanical components of the positioning system are shown. The block scheme and software functional scheme for intelligent neural network system of analysis of the internal microstructure of objects are presented. The method of choice of design parameters of CAD of X-ray microtomography aims at improving the quality of design and reducing costs of it. It is supposed to reduce the design time and eliminate the growing number of engineers involved in development and construction of X-ray microtomographic scanners.展开更多
Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cycloph...Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.展开更多
To improve the transmission accuracy and stiffness of the ball cycloid reducer, the authors developed a novel cycloid ball reducer, which uses a full complement ball as its gear teeth. Ceramic balls are used to get be...To improve the transmission accuracy and stiffness of the ball cycloid reducer, the authors developed a novel cycloid ball reducer, which uses a full complement ball as its gear teeth. Ceramic balls are used to get better performance in severe working conditions. A simple synthesis method was also found to determine the raceway forms and compute the contact forces among the balls and raceways. The Contact Stress Analysis (CSA) computer program was used to optimize the design of the reducer. In this paper, the following topics are covered: (1) Study of the geometry of the raceways. (2) Analyses of the principal curvature of the raceways are also accomplished. In addition, the modification of the raceway is put forward. (3) The contact forces and the reducer efficiency are evaluated. (4) Study of the performance of ceramic balls used in the CBR. A reducer using the above design technique was tested and the performances show that the reducer has high precision and rigidity. An increase of more than 50 percent transmission power was realized in the new gearing.展开更多
With the goal of suggesting dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN), herein we report the molecular docking of an initial set of 556 compounds related to the pyridinone class. Docking with...With the goal of suggesting dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN), herein we report the molecular docking of an initial set of 556 compounds related to the pyridinone class. Docking with multiple crystallographic structures of HIV-1 RT led to 160 potential binders of RT interacting with key amino acid residues at the enzyme’s allosteric site. Compounds selected from the docking with RT were further docked with a crystallographic structure of HIV-1 IN. A total of 31 structures had the potential to make contacts with Mg2+ ions located in a small space between DNA and IN. Interactions with Mg2+ ions are relevant because they participate in the stabilization of the IN-DNA complex. In conclusion, 31 compounds synthetically accessible are proposed as dual inhibitors of RT and IN. It is hypothesized that the suggested compounds will inhibit RT by occupying the allosteric site for NNRTIs and will inhibit the catalytic activity of IN by destabilizing the IN-DNA complex. The main perspective of this work is the synthesis and biological testing of the candidate molecules.展开更多
计算机辅助药物分子设计是现代药物化学研究的重要组成部分,在学术和工业界具有广泛的应用前景。近年来涌现的众多在线工具能够为药物设计教学带来便捷。本文介绍了一系列优秀的免费在线工具,包括Swiss Drug Design、Cavity Plus、Pharm...计算机辅助药物分子设计是现代药物化学研究的重要组成部分,在学术和工业界具有广泛的应用前景。近年来涌现的众多在线工具能够为药物设计教学带来便捷。本文介绍了一系列优秀的免费在线工具,包括Swiss Drug Design、Cavity Plus、Pharm Mapper和ADMETlab,探讨它们在药物分子设计课程中的应用。以环氧合酶2及其抑制剂吲哚美辛为案例,详细展示如何利用这些工具进行药物设计实践。所述方法不仅适用于理论课程的教学演示,还可用于实验课程的实际操作,并可为学生的创新课题研究提供指导。展开更多
文摘The article is to study the development of computer-aided design of X-ray microtomography—the device for investigating the structure and construction of three-dimensional images of organic and inorganic objects on the basis of shadow projections. This article provides basic information regarding CAD of X-ray microtomography and a scheme consisting of three levels. The article also shows basic relations of X-ray computed tomography, the generalized scheme of an X-ray microtomographic scanner. The methods of X-ray imaging of the spatial microstructure and morphometry of materials are described. The main characteristics of an X-ray microtomographic scanner, the X-ray source, X-ray optical elements and mechanical components of the positioning system are shown. The block scheme and software functional scheme for intelligent neural network system of analysis of the internal microstructure of objects are presented. The method of choice of design parameters of CAD of X-ray microtomography aims at improving the quality of design and reducing costs of it. It is supposed to reduce the design time and eliminate the growing number of engineers involved in development and construction of X-ray microtomographic scanners.
文摘Aim: The objects of this study originated from the experimental observations, whereby the HIV -1 gp120 V3 loop is a high-affinity ligand for immunophilins, and consisted in generating the structural complex of cyclophilin (Cyc) B belonging to immunophilins family with the virus subtype A V3 loop (SA-V3 loop) as well as in specifying the Cyc B segment forming the binding site for V3 synthetic copy of which, on the assumption of keeping the 3D peptide structure in the free state, may present a forwardlooking basic structure for anti-AIDS drug development. Methods: To reach the objects of view, molecular docking of the HIV-1 SA-V3 loop structure determined previously with the X-ray conformation of Cyc B was put into practice by Hex 4.5 program (http://www.loria.fr/~ritchied/ hex/) and the immunophilin stretch responsible for binding to V3 (Cyc B peptide) was identified followed by examination of its 3D structure and dynamic behavior in the unbound status. To design the Cyc B peptide, the X-ray conformation for the identical site of the native protein was involved in the calculations as a starting model to find its best energy structural variant. The search for this most preferable structure was carried out by consecutive use of the molecular mechanics and simulated annealing methods. The molecular dynamics computations were implemented for the Cyc B peptide by the GROMACS computer package (http:// www.gromacs.org/). Results: The overmolecular structure of Cyc B with V3 was built by computer modeling tools and the immunophilinderived peptide able to mask effectively the structurally invariant V3 segments embracing the functionally crucial amino acids of the HIV-1 gp120 envelope protein was constructed and analyzed. Conclusions: Starting from the joint analysis of the results derived with those of the literature, the generated peptide was suggested to offer a promising basic structure for making a reality of the protein engineering projects aimed at developing the anti-AIDS drugs able to stop the HIV’s spread.
文摘To improve the transmission accuracy and stiffness of the ball cycloid reducer, the authors developed a novel cycloid ball reducer, which uses a full complement ball as its gear teeth. Ceramic balls are used to get better performance in severe working conditions. A simple synthesis method was also found to determine the raceway forms and compute the contact forces among the balls and raceways. The Contact Stress Analysis (CSA) computer program was used to optimize the design of the reducer. In this paper, the following topics are covered: (1) Study of the geometry of the raceways. (2) Analyses of the principal curvature of the raceways are also accomplished. In addition, the modification of the raceway is put forward. (3) The contact forces and the reducer efficiency are evaluated. (4) Study of the performance of ceramic balls used in the CBR. A reducer using the above design technique was tested and the performances show that the reducer has high precision and rigidity. An increase of more than 50 percent transmission power was realized in the new gearing.
文摘With the goal of suggesting dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN), herein we report the molecular docking of an initial set of 556 compounds related to the pyridinone class. Docking with multiple crystallographic structures of HIV-1 RT led to 160 potential binders of RT interacting with key amino acid residues at the enzyme’s allosteric site. Compounds selected from the docking with RT were further docked with a crystallographic structure of HIV-1 IN. A total of 31 structures had the potential to make contacts with Mg2+ ions located in a small space between DNA and IN. Interactions with Mg2+ ions are relevant because they participate in the stabilization of the IN-DNA complex. In conclusion, 31 compounds synthetically accessible are proposed as dual inhibitors of RT and IN. It is hypothesized that the suggested compounds will inhibit RT by occupying the allosteric site for NNRTIs and will inhibit the catalytic activity of IN by destabilizing the IN-DNA complex. The main perspective of this work is the synthesis and biological testing of the candidate molecules.
基金This work was supported by the National Science and Technology Major Project(2022ZD0115003)the National Natural Science Foundation of China(No.92053202,No.92353304,No.22050003,No.21821004,No.21927901).
文摘计算机辅助药物分子设计是现代药物化学研究的重要组成部分,在学术和工业界具有广泛的应用前景。近年来涌现的众多在线工具能够为药物设计教学带来便捷。本文介绍了一系列优秀的免费在线工具,包括Swiss Drug Design、Cavity Plus、Pharm Mapper和ADMETlab,探讨它们在药物分子设计课程中的应用。以环氧合酶2及其抑制剂吲哚美辛为案例,详细展示如何利用这些工具进行药物设计实践。所述方法不仅适用于理论课程的教学演示,还可用于实验课程的实际操作,并可为学生的创新课题研究提供指导。
