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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在过去的几年中，已经确定了大约200个小蛋白的三维结构和溶液中的DNA低聚物。当与距离几何形状和能量细化计算结合使用时，多维NMR，尤其是二维核过度大冲突效应（2D NOE）光谱，可用于确定DNA片段，小蛋白质和复合物的高分辨率结构。我们研究的主要目的是提高溶液中确定高分辨率蛋白质和核酸结构的能力，包括描绘它们的动态性质。为此，我们一直在开发获得更准确的结构约束（以核对内距离和扭转角的形式）和更多的结构约束。我们目前正在使用限制性分子动力学和颗粒网埃瓦尔德技术制定新的改进协议，这些技术在琥珀色5.0的Sander模块中实现。此外，由于我们主要处理溶液中构型柔性的分子，因此我们一直在探索确定这些分子动态性质的计算方法。出版物-Konerding de，Cheatham Te 3rd，Kollman PA，James TL.：使用粒子网状ewald方法进行溶解的双链DNA的分子动力学。”：生物分子NMR杂志：13：119-31：1999;成就 - 我们在PSC上使用T3E运行了使用Amber 5.0的解释溶剂中DNA的2纳秒不受约束的MD模拟。有关更多详细信息，请参见下面的出版物＃1。 出版物 - 以前没有报道。