The purpose of computer-aided design of new adaptive pulsed arc technologies of welding is: to de- sign optimum algorithms of pulsed control over main energy parameters of welding.It permits:to in- crease welding ...The purpose of computer-aided design of new adaptive pulsed arc technologies of welding is: to de- sign optimum algorithms of pulsed control over main energy parameters of welding.It permits:to in- crease welding productivity, to stabilize the welding regime, to control weld formation,taking into ac- count its spatial position, to proveal specie strength of the welded and coatings. Computer- aided design reduces the time of development of new pulsed arc technology:provides the optimization of technological referes according to the operating conditions of welded joints,the prediction of the ser- vice life of the welds.The developed methodology of computer-aided design of advanced technologies, models, original software, adaptive algorithms of pulsed control, and spend equipment permits to regulate penetration,the weld shape, the sizes of heat - affected zone; to predict sired properties and quality of welded joints.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
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
近年来多巴胺D3受体(DRD_(3))在神经系统疾病的治疗过程中受到大量关注,包括帕金森、精神分裂、药物依赖等。本文综述2015年至今多巴胺D3受体选择性配体的研究进展,并以分子动力学原理为基础,利用Discovery Studio 4.5软件评价了这些配...近年来多巴胺D3受体(DRD_(3))在神经系统疾病的治疗过程中受到大量关注,包括帕金森、精神分裂、药物依赖等。本文综述2015年至今多巴胺D3受体选择性配体的研究进展,并以分子动力学原理为基础,利用Discovery Studio 4.5软件评价了这些配体的选择性,建立了基于分子共同特征的药效团模型,从类药分子库中筛选出对设计新型配体具有先导化合物意义的小分子化合物,以期对D3受体选择性配体的研究提供参考。展开更多
计算机辅助药物设计(Computer-Aided Drug Design,CADD)已成为当今药物研发不可或缺的一部分。采用传统的方法预测小分子结合自由能有一定的局限性,由于传统方法默认了小分子的结构信息与结合能之间是线性的关系,而对于结构-化学信息二...计算机辅助药物设计(Computer-Aided Drug Design,CADD)已成为当今药物研发不可或缺的一部分。采用传统的方法预测小分子结合自由能有一定的局限性,由于传统方法默认了小分子的结构信息与结合能之间是线性的关系,而对于结构-化学信息二者之间并不是线性关系的情况,其预测结果并不是十分准确。随着深度学习技术的发展,我们可以通过神经网络对线性问题或者是非线性问题进行建模,以在小分子的结构信息与其结合能之间建立线性或者非线性的联系,使其预测的结果准确率有所提高。展开更多
Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacopoeia search against a 3D...Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacopoeia search against a 3D structural database of natural products for lead discovery and computer-aided synthesis design for avoiding un useful synthetic experiments. This work demonstrated that computer aided drug design and synthesis design would help us to make the consideration of environmental concerns systematically, rather than having to deal later with the unnecessary waste chemicals. Thus, it is shown that chemical computer-aided design (CAD) is an indispensable part of Green Chemistry.展开更多
文摘The purpose of computer-aided design of new adaptive pulsed arc technologies of welding is: to de- sign optimum algorithms of pulsed control over main energy parameters of welding.It permits:to in- crease welding productivity, to stabilize the welding regime, to control weld formation,taking into ac- count its spatial position, to proveal specie strength of the welded and coatings. Computer- aided design reduces the time of development of new pulsed arc technology:provides the optimization of technological referes according to the operating conditions of welded joints,the prediction of the ser- vice life of the welds.The developed methodology of computer-aided design of advanced technologies, models, original software, adaptive algorithms of pulsed control, and spend equipment permits to regulate penetration,the weld shape, the sizes of heat - affected zone; to predict sired properties and quality of welded joints.
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.
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。
文摘近年来多巴胺D3受体(DRD_(3))在神经系统疾病的治疗过程中受到大量关注,包括帕金森、精神分裂、药物依赖等。本文综述2015年至今多巴胺D3受体选择性配体的研究进展,并以分子动力学原理为基础,利用Discovery Studio 4.5软件评价了这些配体的选择性,建立了基于分子共同特征的药效团模型,从类药分子库中筛选出对设计新型配体具有先导化合物意义的小分子化合物,以期对D3受体选择性配体的研究提供参考。
文摘计算机辅助药物设计(Computer-Aided Drug Design,CADD)已成为当今药物研发不可或缺的一部分。采用传统的方法预测小分子结合自由能有一定的局限性,由于传统方法默认了小分子的结构信息与结合能之间是线性的关系,而对于结构-化学信息二者之间并不是线性关系的情况,其预测结果并不是十分准确。随着深度学习技术的发展,我们可以通过神经网络对线性问题或者是非线性问题进行建模,以在小分子的结构信息与其结合能之间建立线性或者非线性的联系,使其预测的结果准确率有所提高。
基金Special article from the First International workshop on Green Chemistry, the University of ScienceTechnology of China, Hefei, China, May, 1998.Project supported in part by grants from the State Plan Commission of China (No. 96-547-01), the National
文摘Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacopoeia search against a 3D structural database of natural products for lead discovery and computer-aided synthesis design for avoiding un useful synthetic experiments. This work demonstrated that computer aided drug design and synthesis design would help us to make the consideration of environmental concerns systematically, rather than having to deal later with the unnecessary waste chemicals. Thus, it is shown that chemical computer-aided design (CAD) is an indispensable part of Green Chemistry.
