RELAXATION MATRIX REFINEMENT OF THE SOLUTION STRUCTURE OF SQUASH TRYPSIN-INHIBITOR
RELAXATION MATRIX REFINEMENT OF THE SOLUTION STRUCTURE OF SQUASH TRYPSIN-INHIBITOR
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DOI：
10.1016/0022-2836(91)90189-d
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发表时间：
1991-06-05
影响因子：
5.6
通讯作者：
HOLAK, TA
中科院分区：
文献类型：
--
作者：
NILGES, M;HABAZETTL, J;HOLAK, TA
小南瓜胰蛋白酶抑制剂 CMTI-I 的结构是通过直接最小化观察到的二维核 Overhauser 增强 (NOE) 强度与通过完全弛豫矩阵方法计算的强度之间的差异来细化的。为了实现这一点，在分子动力学程序 X-PLOR 的势能函数中添加了与该差异成比例的项。分析计算关于原子坐标的导数。因此，在细化过程中充分考虑了自旋扩散效应。细化的初始结构是最近通过溶液核磁共振确定的，使用孤立的双自旋近似来导出距离范围估计。核磁共振数据的拟合显着改善，在共轭梯度最小化的几个循环期间，精细结构仅发生很小的变化。然而，在模拟退火过程中，构象发生了较大的变化（约 1 Å），同时实验和计算的二维 NOE 强度之间的差异进一步减小。精修后的结构比初始结构更接近与胰蛋白酶复合的抑制剂的X射线结构。初始结构和X射线结构之间主链原子的均方根差为0.96 Å，精化结构和X射线结构之间的主链原子均方根差为0.61 Å。
The structure of the small squash trypsin inhibitor CMTI-I is refined by directly minimizing the difference between the observed two-dimensional nuclear Overhauser enhancement (NOE) intensities and those calculated by the full relaxation matrix approach. To achieve this, a term proportional to this difference was added to the potential energy function of the molecular dynamics program X-PLOR. Derivatives with respect to atomic co-ordinates are calculated analytically. Spin diffusion effects are thus accounted for fully during the refinement. Initial structures for the refinement were those determined recently by solution nuclear magnetic resonance using the isolated two-spin approximation to derive distance range estimates. The fits to the nuclear magnetic resonance data improve significantly with only small shifts in the refined structures during a few cycles of conjugate gradient minimization. However, larger changes (≈ 1 Å) in the conformation occur during simulated annealing, which is accompanied by a further reduction of the difference between experimental and calculated two-dimensional NOE intensities. The refined structures are closer to the X-ray structure of the inhibitor complexed with trypsin than the initial structures. The root-mean-square difference for backbone atoms between the initial structures and the X-ray structure is 0.96 Å, and that between the refined structures and the X-ray structure 0.61 Å.