COMPUTER GRAPHICS EQUIPMENT

这项提议的广泛目标是应用现代计算和 图形方法加速了解决生物问题的进程。这个 这里的重点是两个主要的研究领域。 第一个领域涉及计算机方法的开发和使用 根据序列预测RNA结构。特纳博士的团队正在研究 用于这一目的的计算机方法。新的数据正在获得， 特别是通过使用热力学、二维核磁共振和 化学敏感性研究，这将使进一步完善 这些计算机代码。对这些数据的解释将需要建模 用分子动力学/力学研究涉及的复杂结构 结合三维立体图形显示的计算 能力。林达尔博士还将这些方法应用于 研究核糖体蛋白合成的调节和Dr。 戈洛夫斯基将探索序列-结构-功能关系 四膜虫RNA. 第二个研究领域将使用分子图形学和计算 帮助设计和解释广泛的 生物化学和生物物理实验。参与研究的研究人员(Dr。 Krugh、McLendon、Turner、Kreilick和Kool)将学习结构和 药物与寡核苷酸结合的机制方面(以及其他)， 蛋白质中的电子转移，自剪接RNA，金属酶结构， 和DNA三螺旋的形成。分子动力学模拟和精确 对所涉及的分子进行三维可视化将对 实验的设计与分析。500 MHz二维核磁共振 实验将是这项拟议研究的核心。内部- 来自NOESY数据的分子距离估计将被用来约束 确定三维结构的能量最小化程序 溶液中的生物分子。

The broad objective of this proposal is to apply modern computational and graphics methods to accelerate progress in solving biological problems. The focus here is in two main research areas. The first area involves development and use of computer methods for predicting RNA structure from sequence. Dr. Turner's group is developing computer methods for this purpose. New data are being obtained, particularly through the use of thermodynamics, two-dimensional NMR and chemical susceptibility studies, which will allow further refinements of these computer codes. Interpretation of these data will require modelling the complicated structures involved using molecular dynamics/mechanics calculations coupled with 3-dimensional stereo graphics display capabilities. These methods are also being applied by Dr. Lindahl to investigate regulation of the synthesis of ribosomal proteins and by Dr. Gorovsky to probe sequence - structure - function relationships in tetrahymena RNA. A second area of research will use molecular graphics and computational techniques to aid in the design and interpretation of a wide range of biochemical and biophysical experiments. The researchers involved (Drs. Krugh, McLendon, Turner, Kreilick and Kool) will study structural and mechanistic aspects of (among others) drug binding to oligonucleotides, electron transfer in proteins, self-splicing RNA, metalloenzyme structures, and DNA triple helix formation. Molecular dynamics simulations and accurate 3-dimensional visualization of the molecules involved will be critical for the design and analysis of the experiments. 500 MHz two-dimensional NMR experiments will be central to much of this proposed research. Intra- molecular distance estimates from NOESY data will be used to constrain energy minimization programs to determine the three-dimensional structure of biomolecules in solution.