MOLECULAR DYNAMICS FLEXIBLE FITTING (MDFF)

分子动力学柔性接头 (MDFF)

• 批准号: 8172041
• 负责人: LEONARDO G TRABUCO
• 金额: $ 6.7万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172041
• 关键词: Complex; Computer Retrieval of Information on Scientific Projects Database; Computing Methodologies; Cryoelectron Microscopy; Data; Funding; Grant; Imagery; Institution; Macromolecular Complexes; Maps; Methods; Molecular; Molecular Conformation; Physiological; Research; Research Personnel; Resolution; Resources; Ribosomes; Source; Structure; System; Techniques; United States National Institutes of Health; X-Ray Crystallography; density; flexibility; molecular dynamics; novel; programs; restraint; simulation; simulation software

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cryo-electron microscopy provides density maps of biomolecular complexes in their functional states, but only at low resolution, unlike X-ray crystallography, which provides atomic-resolution structures of biomolecules but usually not in a physiological state. Computational methods to combine information from both techniques hold the promise of generating physiologically accurate, high-resolution structures of biomolecular complexes. To combine experimental data from these two sources, the Resource developed a novel method, molecular dynamics flexible fitting (MDFF; http://www.ks.uiuc.edu/Research/mdff) [1,2], to fit atomic structures into cryo-EM density maps. MDFF employs molecular dynamics (MD) to perform the fitting, which allows flexibility while maintaining a realistic conformation. The standard MD force field is modified by incorporating the EM density map as an attractive potential that drives atoms into high-density regions. Furthermore, restraints are applied to preserve secondary structure of the biomolecules. MDFF setup and analysis are performed with the Resource's molecular visualization program, VMD, and MDFF simulations are conducted using the Resource's MD simulation software, NAMD. Since NAMD is highly scalable and supports simulation of large systems, MDFF can be applied to large macromolecular complexes such as the ribosome [3].

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 冷冻电子显微镜提供了其生物分子复合物的密度图 功能状态，但仅在低分辨率下，与X射线晶体学不同，这 提供生物分子的原子分辨率结构，但通常不在生理中 状态。结合两种技术信息的计算方法 持有产生生理准确，高分辨率结构的承诺 生物分子复合物。为了结合这两个来源的实验数据， 资源开发了一种新颖的方法，即分子动力学柔性拟合（MDFF； http://www.ks.uiuc.edu/research/mdff）[1,2] 密度图。 MDFF采用分子动力学（MD）执行拟合， 这可以在保持逼真的构象的同时灵活。标准 MD力场通过将EM密度图纳入吸引力来修改 将原子驱动到高密度区域的潜力。此外，还采用约束来保存二级结构 生物分子。 MDFF设置和分析 使用资源的分子可视化程序VMD和 MDFF仿真是使用资源的MD仿真软件进行的 namd。由于NAMD具有高度可扩展性，并支持大型系统的模拟，因此 MDFF可以应用于大型大分子复合物，例如核糖体[3]。