A critical assessment of the performance of protein-ligand scoring functions based on NMR chemical shift perturbations.
A critical assessment of the performance of protein-ligand scoring functions based on NMR chemical shift perturbations.
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DOI：
10.1021/jm070484a
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发表时间：
2007-10
影响因子：
7.3
通讯作者：
B. Wang;Lance M. Westerhoff;K. Merz
中科院分区：
文献类型：
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作者：
B. Wang;Lance M. Westerhoff;K. Merz
我们已经产生的FKBP-GPI复杂的对接姿态使用八个对接程序，并比较他们的评分功能与评分的基础上NMR化学位移扰动（NMRScore）。由于化学位移扰动（CSP）对结合口袋内配体的方向非常敏感，NMRScore提供了一种准确而直接的方法来评分不同的姿势。所有的评分功能检查他们的能力，高度排名的天然样结构，并将它们从诱饵产生的蛋白质-配体复合物的姿态。NMRScore的整体性能在这两个方面都远远优于与对接程序相关的基于能量的评分函数。总之，我们发现对接程序与NMR Score的组合产生了一种方法，该方法可以稳健地确定蛋白质-配体复合物的结合位点结构，从而提供了一种新的工具，有助于基于结构的药物发现过程。
We have generated docking poses for the FKBP-GPI complex using eight docking programs, and compared their scoring functions with scoring based on NMR chemical shift perturbations (NMRScore). Because the chemical shift perturbation (CSP) is exquisitely sensitive on the orientation of the ligand inside the binding pocket, NMRScore offers an accurate and straightforward approach to score different poses. All scoring functions were inspected by their abilities to highly rank the native-like structures and separate them from decoy poses generated for a protein-ligand complex. The overall performance of NMRScore is much better than that of energy-based scoring functions associated with docking programs in both aspects. In summary, we find that the combination of docking programs with NMRScore results in an approach that can robustly determine the binding site structure for a protein-ligand complex, thereby providing a new tool facilitating the structure-based drug discovery process.