How to Improve Docking Accuracy of AutoDock4.2: A Case Study Using Different Electrostatic Potentials
How to Improve Docking Accuracy of AutoDock4.2: A Case Study Using Different Electrostatic Potentials
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如何提高AutoDock4.2的对接精度：使用不同静电势的案例研究
DOI：
10.1021/ci300417y
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Li, Minyong
中科院分区：
文献类型：
--
作者：
Hou, Xuben;Du, Jintong;Li, Minyong
分子对接是预测配体与受体结合构象和结合能的重要手段，构建了高通量的虚拟筛选技术。到目前为止，已经发布了越来越多的分子对接程序，其中AutoDock 4.2是一个广泛使用的对接程序，具有出色的准确性。部分电荷的计算是精确构象搜索和结合能估算的基础。然而，尚未确定静电电位对AutoDock 4.2对接精度的显著性的系统比较。本文利用AutoDock 4. 2软件对AM 1-BCC、Del-Re、formal、Gasteiger-Hückel、Gasteiger-Marsili、Hückel、Merck分子力场（MMFF）和普尔曼等9种不同的电荷分配方法以及从头算Hartree-Fock电荷进行了研究。结果表明，经验Gasteiger-Hückel模型最适用于大型数据库的虚拟筛选;半经验AM 1-BCC模型适用于小型数据库的先导化合物优化和精确虚拟筛选。
Molecular docking, which is the indispensable emphasis in predicting binding conformations and energies of ligands to receptors, constructs the high-throughput virtual screening available. So far, increasingly numerous molecular docking programs have been released, and among them, AutoDock 4.2 is a widely used docking program with exceptional accuracy. It has heretofore been substantiated that the calculation of partial charge is very fundamental for the accurate conformation search and binding energy estimation. However, no systematic comparison of the significances of electrostatic potentials on docking accuracy of AutoDock 4.2 has been determined. In this paper, nine different charge-assigning methods, including AM1-BCC, Del-Re, formal, Gasteiger-Hückel, Gasteiger-Marsili, Hückel, Merck molecular force field (MMFF), and Pullman, as well as the ab initio Hartree-Fock charge, were sufficiently explored for their molecular docking performance by using AutoDock4.2. The results clearly demonstrated that the empirical Gasteiger-Hückel charge is the most applicable in virtual screening for large database; meanwhile, the semiempirical AM1-BCC charge is practicable in lead compound optimization as well as accurate virtual screening for small databases.