LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites
LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites
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DOI：
10.1016/s1093-3263(02)00164-x
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
Waldman, M
中科院分区：
文献类型：
--
作者：
Venkatachalam, CM;Jiang, X;Waldman, M
我们提出了一种新的基于形状的方法，LigandFit，准确对接到蛋白质活性位点的配体。该方法采用空腔检测算法来检测蛋白质中的内陷作为候选活性位点区域。形状比较过滤器与蒙特卡罗构象搜索相结合，用于生成与活性位点形状一致的配体姿势。候选人的姿态最小化的背景下，使用基于网格的方法来评估蛋白质-配体相互作用能的活性位点。使用新的非线性插值方案，大大减少了网格插值产生的误差。结果提出了19种不同的蛋白质-配体复合物。该方法看起来很有前途，在19个复合物中的14个中再现了2埃RMS内的X射线结构配体位姿。还介绍了一项应用于胸苷激酶受体的高通量筛选研究，其中LigandFit与LigScore（一种内部开发的评分函数[1]）结合使用时，对接种有已知活性物质的配体池产生了非常好的命中率。(C)2002年由Elsevier Science Inc.出版
We present a new shape-based method, LigandFit, for accurately docking ligands into protein active sites. The method employs a cavity detection algorithm for detecting invaginations in the protein as candidate active site regions. A shape comparison filter is combined with a Monte Carlo conformational search for generating ligand poses consistent with the active site shape. Candidate poses are minimized in the context of the active site using a grid-based method for evaluating protein-ligand interaction energies. Errors arising from grid interpolation are dramatically reduced using a new non-linear interpolation scheme. Results are presented for 19 diverse protein-ligand complexes. The method appears quite promising, reproducing the X-ray structure ligand pose within an RMS of 2Angstrom in 14 out of the 19 complexes. A high-throughput screening study applied to the thymidine kinase receptor is also presented in which LigandFit, when combined with LigScore, an internally developed scoring function [1], yields very good hit rates for a ligand pool seeded with known actives. (C) 2002 Published by Elsevier Science Inc.