APPLICATION OF MOLECULAR-DYNAMICS WITH INTERPROTON DISTANCE RESTRAINTS TO 3-DIMENSIONAL PROTEIN-STRUCTURE DETERMINATION - A MODEL STUDY OF CRAMBIN
APPLICATION OF MOLECULAR-DYNAMICS WITH INTERPROTON DISTANCE RESTRAINTS TO 3-DIMENSIONAL PROTEIN-STRUCTURE DETERMINATION - A MODEL STUDY OF CRAMBIN
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DOI：
10.1016/0022-2836(86)90146-4
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发表时间：
1986-10-05
影响因子：
5.6
通讯作者：
GRONENBORN, AM
中科院分区：
文献类型：
--
作者：
CLORE, GM;BRUNGER, AT;GRONENBORN, AM
基于短的质子间距离（<4埃），限制分子动力学用于确定三维蛋白质结构的适用性。可以从溶液中的核磁共振测量实际地确定。使用的模型系统是1.2.ANG。46个残基的蛋白质crambin的分辨率晶体结构，从其中一组240个近似距离限制，分为三个范围（2.5 ±. 0.5，. **图形 **。和4.+-. 1.ANG），导出了该质子间距离组包括159个短程（i. sbd. j ≤ 0. 5)以及56个（i. sbd. j> 5）长范围残基间距离和25个残基内距离。使用从两个初始结构开始的许多不同的方案进行受约束的分子动力学：完全扩展的β-链;和具有两个α-在与晶体结构中相同位置的螺旋（残基7至19，和23至30）和所有其它的延伸β-螺旋形式的残基股。均方根（r.m.s.）这两种初始结构和晶体结构之间的原子差为43埃。和23.分别它示出，提供的协议被使用，允许二级结构元素形成至少部分折叠成三级结构之前，收敛到正确的最终结构，全球和本地，实现。均方根收敛的约束动力学结构和晶体结构之间的原子差在1.5至2.2埃的范围内。对于主链原子，和2.0至2.8埃。对于所有原子。均方根X射线结构和通过首先平均收敛的约束动力学结构的坐标而获得的结构之间的原子差异甚至更小：对于主链原子和1.6埃。对于所有原子。这些结果提供了一个衡量未来的实验结果的蛋白质的晶体结构是未知的。此外，从检查的动力学轨迹，它示出的收敛途径，其次是各种模拟是不同的。
The applicability of restrained molecular dynamics for the determination of three-dimensional protein structures on the basis of short interproton distances (< 4 .ANG.) that can be realistically determined from nuclear magnetic resonance measurements in solution is assessed. The model system used is the 1.2 .ANG. resolution crystal structure of the 46 residue protein crambin, from which a set of 240 approximate distance restraints, divided into three ranges (2.5 .+-. 0.5, .**GRAPHIC**. and 4 .+-. 1 .ANG.), is derived. This interproton distance set comprises 159 short-range ( i.sbd.j .ltoreq. 5) and 56 ( i.sbd.j > 5) long-range inter-residue distances and 25 intra-residue distances. Restrained molecular dynamics are carried out using a number of different protocols starting from two initial structures: a completely extended .beta.-strand; and an extended structure with two .alpha.-helices in the same positions as in the crystal structure (residues 7 to 19, and 23 to 30) and all other residues in the form of extended .beta.-strands. The root-mean-square (r.m.s.) atomic differences between these two initial structures and the crystal structure are 43 .ANG. and 23 .ANG., respectively. It is shown that, provided protocols are used that permit the secondary structure elements to form at least partially prior to folding into a tertiary structure, convergence to the correct final structure, both globally and locally, is achieved. The r.m.s. atomic differences between the converged restrained dynamics structures and the crystal structure range from 1.5 to 2.2 .ANG. for the backbone atoms and from 2.0 to 2.8 .ANG. for all atoms. The r.m.s. atomic difference between the X-ray structure and the structure obtained by first averaging the co-ordinates of the converged restrained dynamics structures is even smaller: 1.0 .ANG. for the backbone atoms and 1.6 .ANG. for all atoms. These results provide a measure with which to judge future experimental results on proteins whose crystal structures are unknown. In addition, from an examination of the dynamics trajectories, it is shown that the convergence pathways followed by the various simulations are different.