Novel procedure for modeling ligand/receptor induced fit effects
Novel procedure for modeling ligand/receptor induced fit effects
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DOI：
10.1021/jm050540c
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发表时间：
2006-01-26
影响因子：
7.3
通讯作者：
Farid, R
中科院分区：
文献类型：
--
作者：
Sherman, W;Day, T;Farid, R
我们提出了一种新的蛋白质-配体对接方法，准确地占配体和受体的灵活性，通过迭代结合刚性受体对接（滑翔）与蛋白质结构预测（总理）技术。虽然当受体结构在配体结合时基本上不改变时，传统的刚性受体对接方法是有用的，但是当蛋白质必须被“诱导”成针对给定配体的正确结合构象时，成功是有限的。我们提供了一个深入的描述，我们的新方法，目前的结果为21个药学相关的例子。传统的刚性受体对接这21例产生的平均RMSD为5.5埃。对于21对，用于对接到柔性受体的平均配体RMSD是1.4埃; RMSD是1.5埃。
We present a novel protein-ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does not change substantially upon ligand binding, success is limited when the protein must be "induced" into the correct binding conformation for a given ligand. We provide an in-depth description of our novel methodology and present results for 21 pharmaceutically relevant examples. Traditional rigid-receptor docking for these 21 cases yields an average RMSD of 5.5 angstrom. The average ligand RMSD for docking to a flexible receptor for the 21 pairs is 1.4 angstrom; the RMSD is