DYNAMIC MACROMOLECULAR STRUCTURES IN SOLUTION VIA ANALYSIS OF NMR EXPERIMENTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在过去的几年中，已经确定了溶液中大约200种小蛋白质和DNA寡聚体的三维结构。多维NMR，特别是二维核Overhauser效应（2D NOE）谱，当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，以获得更准确的结构约束（以核间距和扭转角的形式）和更多的结构约束。我们目前正在研究新的改进协议，使用约束分子动力学和粒子网格埃瓦尔德技术，在砂光机模块的琥珀5.0。此外，由于我们主要处理溶液中的构象灵活的分子，我们一直在探索确定这些分子的动力学性质的计算方法。出版物- Konerding DE，Cheatham TE 3rd，Kollman PA，James TL.：“使用粒子网格埃瓦尔德方法的溶剂化双链DNA的约束分子动力学。“：Journal of Biomolecular NMR：13：119-31：1999;成就-我们使用PSC的T3 E，使用AMBER 5.0在显式溶剂中运行DNA的2纳秒无限制MD模拟。请参阅下面的出版物#1了解更多详情。 出版物-以前没有报告过。

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.