MOLECULAR DYNAMICS SIMULATIONS OF BIOLOGICAL MACROMOLECULES

生物大分子的分子动力学模拟

• 批准号: 3838543
• 负责人: B R BROOKS
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838543
• 关键词: CD4 molecule; HIV envelope protein gp120; RNA directed DNA polymerase; X ray crystallography; alanine; bacterial proteins; chemical models; computer data analysis; computer simulation; deuterium; endopeptidases; human immunodeficiency virus 1; interleukin 1; intermolecular interaction; lipid bilayer membrane; lysozyme; macromolecule; model design /development; molecular dynamics; myoglobin; nuclear magnetic resonance spectroscopy; nuclease; physical model; protein structure; protein structure function; virus protein

Applied theoretical research on AIDS proteins and other molecules ofbiomedical interest as well as basic research involving macromolecules is in progress. Molecular dynamics simulations of AIDS proteins involve projects directly related to the NIH Intramural AIDS Targeted Antiviral Program. The general goal is to understand binding interactions with HIV-1 proteins in order to facilitate the design of drugs which may interfere with the spread of the virus. Important therapeutic targets under study include HIV-1 reverse transcriptase, HIV-1 protease, the HIV-1 envelope protein gp120, and the CD4 receptor protein found on certain host cells. Projects include modeling of leucine zippers in GCN4 and HIV-1 reverse transcriptase, simulations of HIV-1 protease monomer in solution, analysis of inhibitor binding to the active site of HIV-1 protease, and investigation of the mechanism of action of HIV-1 protease. Other applied research on molecules of biomedical interest uses molecular dynamics simulations to predict function or structures of peptides and proteins. Projects include modeling the metabolism-based transformation of myoglobin to an oxidase and the simulation of lattice vibrations in the L-alanine crystal. Basic research is under way to provide a better understanding of biochemical systems. Projects include studies of environmental effects on protein dynamics, a simulation study of interleukin 1-beta, comparison with crystallographic and NMR data, harmonic analysis of large systems, modeling and simulation of lipid bilayers (gel and crystal phases in particular), structural analysis of T4 lysozyme mutants in the harmonic limit, comparison of simulations on staphylococcal nuclease with NMR data, and the examination of long range deuterium isotope effects in C-13 NMR spectra.

艾滋病蛋白等分子的应用理论研究 生物医学兴趣以及涉及大分子的基础研究 正在进行 艾滋病蛋白质的分子动力学模拟涉及项目 与NIH校内艾滋病靶向抗病毒计划直接相关。 总的目标是了解与HIV-1的结合相互作用 蛋白质，以促进药物的设计， 病毒的传播。 下的重要治疗靶点 研究包括HIV-1逆转录酶、HIV-1蛋白酶、HIV-1 包膜蛋白gp 120，以及在某些 宿主细胞 项目包括GCN 4中亮氨酸拉链的建模， HIV-1逆转录酶，模拟HIV-1蛋白酶单体， 溶液，分析与HIV-1活性位点结合的抑制剂 蛋白酶，并研究HIV-1的作用机制 蛋白酶 生物医学分子的其他应用研究 分子动力学模拟预测功能或结构 肽和蛋白质。项目包括建立基于代谢的 肌红蛋白向氧化酶的转化及晶格模拟 L-丙氨酸晶体的振动 正在进行基础研究，以便更好地了解 生化系统 项目包括环境影响研究 蛋白质动力学，白细胞介素1-β的模拟研究， 与晶体学和NMR数据的比较， 大型系统，脂质双层（凝胶和晶体）的建模和模拟 特别是阶段），T4溶菌酶突变体的结构分析 调和极限，葡萄球菌核酸酶模拟与 核磁共振数据，以及长程氘同位素效应的检验 在C-13 NMR谱中。