DETERMINATION OF 3-DIMENSIONAL STRUCTURES OF PROTEINS FROM INTERPROTON DISTANCE DATA BY HYBRID DISTANCE GEOMETRY-DYNAMICAL SIMULATED ANNEALING CALCULATIONS
DETERMINATION OF 3-DIMENSIONAL STRUCTURES OF PROTEINS FROM INTERPROTON DISTANCE DATA BY HYBRID DISTANCE GEOMETRY-DYNAMICAL SIMULATED ANNEALING CALCULATIONS
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DOI：
10.1016/0014-5793(88)81148-7
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发表时间：
1988-03-14
期刊：
影响因子：
3.5
通讯作者：
GRONENBORN, AM
中科院分区：
文献类型：
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作者：
NILGES, M;CLORE, GM;GRONENBORN, AM
基于质子间距离约束，提出了一种新的确定蛋白质三维结构的距离空间-实空间混合方法。它包括以下步骤：（i）通过使用称为“嵌入”的程序从多维距离空间投影到三维笛卡尔坐标空间中来产生仅包含原子的小子集的一组子结构，从而获得近似多肽折叠;（ii）然后通过每次一个残基最佳拟合延伸的氨基酸来将所有剩余的原子添加到子结构;（iii）所得结构用作真实的空间动力学模拟退火计算的起点。后者涉及将系统加热到高温，然后缓慢冷却，以便克服沿着朝向全局最小区域的路径的势垒。这是通过求解牛顿运动方程来实现的。然而，与传统的约束分子动力学不同，非键相互作用由简单的货车德瓦尔斯排斥项表示。该方法是说明通过计算crambin（46个残基）和球状结构域的组蛋白H5（79个残基）。结果表明，混合方法是更有效的计算和样品的构象空间与实验数据相一致的更大的区域比完整的度量矩阵距离几何计算单独，特别是对于大型系统。
A new hybrid distance space-real space method for determining three-dimensional structures of proteins on the basis of interproton distance restraints is presented. It involves the following steps: (i) the approximate polypeptide fold is obtained by generating a set of substructures comprising only a small subset of atoms by projection from multi-dimensional distance space into three-dimensional cartesian coordinate space using a procedure known as ‘embedding’; (ii) all remaining atoms are then added by best fitting extended amino acids one residue at a time to the substructures; (iii) the resulting structures are used as the starting point for real space dynamical simulated annealing calculations. The latter involve heating the system to a high temperature followed by slow cooling in order to overcome potential barriers along the pathway towards the global minimum region. This is carried out by solving Newton's equations of motion. Unlike conventional restrained molecular dynamics, however, the non-bonded interactions are represented by a simple van der Waals repulsion term. The method is illustrated by calculations on crambin (46 residues) and the globular domain of histone H5 (79 residues). It is shown that the hybrid method is more efficient computationally and samples a larger region of conformational space consistent with the experimental data than full metric matrix distance geometry calculations alone, particularly for large systems.