A fast protein-ligand docking algorithm based on hydrogen bond matching and surface shape complementarity
A fast protein-ligand docking algorithm based on hydrogen bond matching and surface shape complementarity
复制标题
基于氢键匹配和表面形状互补的快速蛋白质-配体对接算法
DOI：
10.1007/s00894-009-0598-7
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发表时间：
2010-05
影响因子：
2.2
通讯作者：
Luo, Wenjia
中科院分区：
文献类型：
--
作者：
Zhu, Yushan;Pei, Jianfeng;Luo, Wenjia
随着人类疾病靶蛋白结构测定的快速发展，基于高通量虚拟筛选的药物发现方法逐渐流行起来。提出了一种基于氢键匹配和表面形状互补的快速对接算法（H-DOCK）。在H-DOCK中，首先采用基于分治策略的枚举方法，通过最大化配体与蛋白质之间的氢键匹配度来对配体与蛋白质之间的分子间模式进行排序，然后根据匹配的氢键几何构型计算配体的对接构象，最后采用一个简单有效的主要反映货车范德华力的评分函数来评价配体的对接构象.对H-DOCK进行了刚性配体对接和柔性配体对接的测试，后者是通过对小分子的多种构象重复刚性对接并将其排列在一起来实现的。对于刚性配体，H-DOCK在一组271个复合物上进行了测试，其中至少有一个分子间氢键，H-DOCK的成功率（RMSD<2.0）为91.1%。对于柔性配体，H-DOCK在另一组93个复合物上进行了测试，其中每个案例都是包含天然配体构象以及AutoDock生成的100个诱饵构象的构象集合[1]，成功率达到81.7%。H-DOCK的高成功率表明氢键和空间位阻可以抓住蛋白质与配体之间的关键相互作用。与传统的对接算法相比，H-DOCK的效率非常高，刚性配体对接平均耗时约0.14秒，柔性配体对接平均耗时约8.25秒。根据初步的对接结果，这意味着H-DOCK可以潜在地用于大规模的虚拟筛选，作为一个预过滤器，更准确，但效率较低的对接算法。
With the rapid development of structural determination of target proteins for human diseases, high throughout virtual screening based drug discovery is gaining popularity gradually. In this paper, a fast docking algorithm (H-DOCK) based on hydrogen bond matching and surface shape complementarity was developed. In H-DOCK, firstly a divide-and-conquer strategy based enumeration approach is applied to rank the intermolecular modes between protein and ligand by maximizing their hydrogen bonds matching, then each docked conformation of the ligand is calculated according to the matched hydrogen bonding geometry, finally a simple but effective scoring function reflecting mainly the van der Waals interaction is used to evaluate the docked conformations of the ligand. H-DOCK is tested for rigid ligand docking and flexible one, the latter is implemented by repeating rigid docking for multiple conformations of a small molecule and ranking all together. For rigid ligands, H-DOCK was tested on a set of 271 complexes where there is at least one intermolecular hydrogen bond, and H-DOCK achieved success rate (RMSD<2.0 Å) of 91.1%. For flexible ligands, H-DOCK was tested on another set of 93 complexes, where each case was a conformation ensemble containing native ligand conformation as well as 100 decoy ones generated by AutoDock [1], and the success rate reached 81.7%. The high success rate of H-DOCK indicates that the hydrogen bonding and steric hindrance can grasp the key interaction between protein and ligand. H-DOCK is quite efficient compared with the conventional docking algorithms, and it takes only about 0.14 seconds for a rigid ligand docking and about 8.25 seconds for a flexible one on average. According to the preliminary docking results, it implies that H-DOCK can be potentially used for large scale virtual screening as a pre-filter for a more accurate but less efficient docking algorithm.
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影响因子：
3
作者：
D. Ritchie;G. Kemp
通讯作者：
D. Ritchie;G. Kemp
影响因子：
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作者：
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