Are time-averaged restraints necessary for nuclear magnetic resonance refinement? A model study for DNA.
Are time-averaged restraints necessary for nuclear magnetic resonance refinement? A model study for DNA.
复制标题
核磁共振精细化是否需要时间平均约束？
DOI：
10.1016/0022-2836(91)90024-z
复制
发表时间：
1991
影响因子：
5.6
通讯作者：
Kollman,PA
中科院分区：
文献类型：
--
作者：
Pearlman,DA;Kollman,PA
最近提出的一种改进方法，从二维核磁共振实验中获得的结构数据，使用分子动力学（MD）进行了探讨。在该方法中，从MD轨迹计算的分子的适当内部坐标的时间平均值由朝向实验目标值的约束驱动。这与目前使用的大多数细化程序形成对比，其中基于适当坐标的瞬时值施加约束。这两种细化方法都适用于theEcoRI限制性位点DNA六聚体d（GAATTC）2，使用目标核奥弗豪泽增强距离来自一纳秒无约束的MD模拟这种结构。将得到的精细结构与作为我们的“实验”数据的无约束MD轨迹的结果进行比较。我们表明，虽然这两种方法可以产生一个平均结构与正确的总体形态，新的方法既允许一个更现实的画面固有的灵活性，并更好地再现精细的构象细节，如序列依赖性。我们还分析了这里产生的非常长的MD轨迹（比任何以前报道的DNA寡聚体更长），并发现显着较短的模拟，通常是那些经常进行的，可能不会产生可接受的可靠值为某些结构参数。
A recently suggested method for refinement of structural data obtained from two-dimensional nuclear magnetic resonance experiments using molecular dynamics (MD) is explored. In this method, the time-averaged values of the appropriate internal co-ordinates of the molecule, calculated from the MD trajectory, are driven by restraints towards the experimental target values. This contrasts with most refinement procedures currently in use, where restraints are applied based on the instantaneous values of the appropriate co-ordinates. Both refinement methods are applied to theEcoRI restriction site DNA hexamer d(GAATTC)2, using target nuclear Overhauser enhancement distances derived from a one nanosecond unrestrained MD simulation of this structure. The resulting refined structures are compared to the results of the unrestrained MD trajectory, which serves as our “experimental” data. We show that although both methods can yield an average structure with the correct gross morphology, the new method allows both a much more realistic picture of inherent flexibility, and reproduces fine conformational detail better, such as sequence dependency. We also analyze the very long MD trajectory generated here (longer than any previously reported for a DNA oligomer), and find that significantly shorter simulations, typical of those frequently performed, may not yield acceptably reliable values for certain structural parameters.