DYNAMIC STRUCTURE OF BIOMOLECULES IN SOLUTION

许多生物分子在溶液中是柔性的。 这可以 通过核磁共振（NMR）方法评估。 事实上，J 标量耦合常数和核Overhauser效应（NOE）数据是 当构象异构体存在于 溶液 在这种情况下，可能无法拟合所有观察到的 单分子构象的NMR参数。 我们有 开发了一个程序，PDQPRO（二次概率分布 PROgramming），它确定最佳概率分布 通过找到最佳拟合， 计算的和实验的核磁共振参数之间。 这种方法需要一种独立的抽样方法， 一组潜在的构象异构体 几种柔性测试的分析 分子与模拟NMR数据表明，PDQPRO能够 识别正确的构象异构体， 计算正确的概率，前提是这些正确的概率 构象异构体存在于潜在结构库中。 目前 我们正在研究PDQPRO的性能， 各种取样方法。 特别是，我们使用了MDtar Torda等人开发的方法，用于生成MD轨迹 柔性RNA环。 MDtar的轨迹总体上解释了 现有的NMR数据;然而，MD轨迹不是很适合 一个全面的结构分析，因为它的大小。 应用 的PDQPRO到这个轨迹减少了一个数量级， 解释实验数据所需的构象数。 的 计算机图形学实验室的资源是必要的，我们的项目 的图形表示的结构合奏，这是一个 重要的问题 特别是，我们正在使用一些 由Eric Pettersen为此特殊目的编写的MidasPlus委托 还有大卫·科内尔丁

Many biological molecules are flexible in solution. This can be assessed by nuclear magnetic resonance (NMR) methods. Indeed, J scalar coupling constants and nuclear Overhauser effect (NOE) data are subject to different types of averaging when conformers are present in solution. In suc a case, it may not be possible to fit all observed NMR parameters with a single molecular conformation. We have developed a program, PDQPRO (Probability Distribution by Quadratic PROgramming), which determines the optimal probability distribution for a predefined pool of potential conformers by finding the best fit between calculated and experimental NMR parameters. Such an approach requires an independent sampling method producing a set of potential conformers. Analysis of a number of flexible test molecules with simulated NMR data has demonstrated that PDQPRO is able to recognize the correct conformers and calculate the correct probabilities, provided that those correct conformers are present in the pool of potential structures. Presently we are investigating the performance of PDQPRO in combination with various sampling methods. In particular, we have used the MDtar method developed by Torda et al. to generate an MD trajectory for a flexible RNA loop. The MDtar trajectory as a whole explained the existing NMR data; however, MD trajectories are not very suitable for a comprehensive structural analysis due to its size. The application of the PDQPRO to this trajectory reduced by an order of magnitude the number of conformers required to explain the experimental data. The Computer Graphics Laboratory resources are necessary for our project for graphical representation of structural ensembles, which is a non-trivial problem. In particular, we are using a number of MidasPlus delegates written for this special purpose by Eric Pettersen and David Konerding.