Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
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DOI：
10.1021/jm0306430
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发表时间：
2004-03-25
影响因子：
7.3
通讯作者：
Shenkin, PS
中科院分区：
文献类型：
--
作者：
Friesner, RA;Banks, JL;Shenkin, PS
与将配体对接到已知蛋白质受体的刚性3D结构的其他方法不同，Glide近似于对接配体的构象、取向和位置空间的完整系统搜索。在这个搜索中，一个初始的粗略定位和评分阶段，大大缩小了搜索空间，其次是扭转灵活的能量优化OPLS-AA非键合电位网格上的几百个幸存的候选人构成。最好的候选者通过姿势构造的蒙特卡罗采样进一步细化;在某些情况下，这对于获得准确的对接姿势至关重要。最佳停靠姿势的选择使用结合经验和基于力场的项的模型能量函数。对接的准确性进行了评估，从282共结晶PDB复合物从构象优化的配体几何形状，不承担正确对接的姿势记忆配体重新对接。排名靠前的姿势的几何误差在近一半的情况下小于1埃，并且仅在其中的约三分之一中大于2埃。与已发表的均方根偏差数据的比较表明，对于具有多达20个可旋转键的配体，Glide的准确度几乎是GOLD的两倍，并且是FlexX的两倍多。Glide也被发现比最近描述的Surflex方法更准确。
Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor, Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand. In this search, an initial rough positioning and scoring phase that dramatically narrows the search space is followed by torsionally flexible energy optimization on an OPLS-AA nonbonded potential grid for a few hundred surviving candidate poses. The very best candidates are further refined via a Monte Carlo sampling of pose conformation; in some cases, this is crucial to obtaining an accurate docked pose. Selection of the best docked pose uses a model energy function that combines empirical and force-field-based terms. Docking accuracy is assessed by redocking ligands from 282 cocrystallized PDB complexes starting from conformationally optimized ligand geometries that bear no memory of the correctly docked pose. Errors in geometry for the top-ranked pose are less than 1 Angstrom in nearly half of the cases and are greater than 2 Angstrom in only about one-third of them. Comparisons to published data on rms deviations show that Glide is nearly twice as accurate as GOLD and more than twice as accurate as FlexX for ligands having up to 20 rotatable bonds. Glide is also found to be more accurate than the recently described Surflex method.