MOLECULAR DOCKING USING SHAPE DESCRIPTORS
MOLECULAR DOCKING USING SHAPE DESCRIPTORS
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DOI：
10.1002/jcc.540130311
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发表时间：
1992-04-01
影响因子：
3
通讯作者：
KUNTZ, ID
中科院分区：
文献类型：
--
作者：
SHOICHET, BK;BODIAN, DL;KUNTZ, ID
分子对接探索两个相互作用分子的结合模式。该技术在研究蛋白质-配体相互作用和药物设计方面越来越受欢迎。分子对接的一个基本问题是取向空间非常大，并且随着相互作用分子的自由度数组合增长。在这里，我们描述和评估可提高基于形状的对接方法的效率和准确性的算法。我们使用分子组织和采样技术来消除对接计算中对分子大小的指数时间依赖性。新技术使我们能够研究对于原始方法而言过于庞大的系统。新算法在 10 个不同的蛋白质配体系统中进行了测试，其中包括 7 个配体本身就是蛋白质的系统。在所有情况下，新算法都成功地重现了蛋白质中实验确定的配体构型。
Molecular docking explores the binding modes of two interacting molecules. The technique is increasingly popular for studying protein-ligand interactions and for drug design. A fundamental problem with molecular docking is that orientation space is very large and grows combinatorially with the number of degrees of freedom of the interacting molecules. Here, we describe and evaluate algorithms that improve the efficiency and accuracy of a shape-based docking method. We use molecular organization and sampling techniques to remove the exponential time dependence on molecular size in docking calculations. The new techniques allow us to study systems that were prohibitively large for the original method. The new algorithms are tested in 10 different protein-ligand systems, including 7 systems where the ligand is itself a protein. In all cases, the new algorithms successfully reproduce the experimentally determined configurations of the ligand in the protein.