DYNAMIC MACROMOLECULAR STRUCTURES IN SOLUTION VIA ANALYSIS OF NMR EXPERIMENTS

通过核磁共振实验分析溶液中的动态大分子结构

• 批准号: 8364211
• 负责人: THOMAS L JAMES
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364211
• 关键词: Achievement; Biomedical Research; CD3E gene; Computing Methodologies; DNA; DNA Structure; Funding; Goals; Grant; High Performance Computing; Journals; Methods; Molecular Structure; National Center for Research Resources; Nature; Nuclear; Principal Investigator; Proteins; Protocols documentation; Publications; Reporting; Research; Research Infrastructure; Resolution; Resources; Running; Solutions; Solvents; Source; Techniques; Torsion; United States National Institutes of Health; Work; cost; flexibility; improved; molecular dynamics; nanosecond; nucleic acid structure; particle; protein complex; research study; restraint; simulation; three dimensional structure; two-dimensional

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the past few years, three-dimensional structures of about 200 small proteins and a DNA oligomers in solution have been determined. Multi-dimensional NMR, in particular two-dimensional nuclear Overhauser effect(2D NOE) spectra, when used in conjunction with distance geometry and energy refinement calculations can be used to determine the high-resolution structure of DNA fragments, small proteins and complexes. A major goal of our research is to improve the capability for determining high-resolution protein and nucleic acid structures in solution, including a depiction of their dynamic nature. To this end, we have been developing methods to obtain more accurate structural restraints(in the form of internuclear distances and torsion angles) and a greater number of structural restraints. We are currently working on new refinement protocols using restrained molecular dynamics and the particle mesh Ewald technique as implemented in the sander module of AMBER 5.0. In addition, as we deal mostly with conformationally flexible molecules in solution, we have been exploring computational methodologies for ascertaining the dynamic nature of these molecules. Publications - Konerding DE, Cheatham TE 3rd, Kollman PA, James TL.:"Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method.":Journal of Biomolecular Nmr:13:119-31:1999; Achievements - We used the T3E at PSC to run a 2 nanosecond unrestrained MD simulation of DNA in explict solvent using AMBER 5.0. See publication #1 below for more details. Publications - None that have not previously been reported.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 在过去的几年里，大约200种小蛋白质和DNA寡聚体在溶液中的三维结构已经被确定。多维 NMR，特别是二维核奥弗豪塞效应 (2D NOE) 谱，与距离几何和能量细化计算结合使用时，可用于确定 DNA 片段、小蛋白质和复合物的高分辨率结构。我们研究的一个主要目标是提高确定溶液中高分辨率蛋白质和核酸结构的能力，包括描述其动态性质。为此，我们一直在开发方法来获得更准确的结构约束（以核间距离和扭转角的形式）和更多数量的结构约束。我们目前正在研究使用约束分子动力学和粒子网格 Ewald 技术的新细化协议，如 AMBER 5.0 的打磨模块中所实施。此外，由于我们主要处理溶液中的构象柔性分子，因此我们一直在探索计算方法来确定这些分子的动态性质。出版物 - Konerding DE、Cheatham TE 3rd、Kollman PA、James TL.：“使用粒子网格 Ewald 方法限制溶剂化双链 DNA 的分子动力学。”：生物分子 Nmr 杂志：13：119-31：1999；成就 - 我们使用 PSC 的 T3E 使用 AMBER 5.0 在显式溶剂中对 DNA 进行 2 纳秒无限制 MD 模拟。有关更多详细信息，请参阅下面的出版物 #1。 出版物 - 以前没有报道过的出版物。