DINC: a new AutoDock-based protocol for docking large ligands.
DINC: a new AutoDock-based protocol for docking large ligands.
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DOI：
10.1186/1472-6807-13-s1-s11
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发表时间：
2013
影响因子：
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通讯作者：
Kavraki LE
中科院分区：
文献类型：
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作者：
Dhanik A;McMurray JS;Kavraki LE
使用流行的程序AutoDock，计算机辅助对接具有6个或更少可旋转键的小配体，相当快和准确。然而，使用AutoDock推荐的标准对接协议对接大型配体的精度较低，计算速度也较慢。在我们早期的工作中，我们提出了一种新的基于AutoDock的增量协议(DINC)，该协议通过改进大型配体的对接来解决AutoDock标准协议的局限性。我们的协议不像标准协议中那样在一个步骤中将大配体对接到目标蛋白质上，而是以增量的方式对接大配体。在本文中，我们提供了三个使用DINC进行对接的详细示例，并将对接结果与使用AutoDock的标准协议获得的结果进行了比较。我们总结了73个由大配体组成的蛋白质-配体复合体的对接研究结果。我们证明了DINC不仅比AutoDock的标准协议快2个数量级，而且在不牺牲对接精度的情况下实现了加速。我们还表明，位置约束可以应用于使用DINC的大配体：这在计算配体的对接构象时很有用。最后，我们介绍了一个使用DINC对接大型配体的Web服务器。使用DINC对接大型配体的速度比AutoDock的标准协议快得多，而不会损失任何准确性。因此，DINC可以作为对接大配体的替代方案。DINC已作为Web服务器实现，并可在http://dinc.kavrakilab.org.上获得治疗性药物设计、合理的疫苗设计和其他涉及大配体的应用可以从DINC及其网络服务器的实现中受益。
Using the popular program AutoDock, computer-aided docking of small ligands with 6 or fewer rotatable bonds, is reasonably fast and accurate. However, docking large ligands using AutoDock's recommended standard docking protocol is less accurate and computationally slow. In our earlier work, we presented a novel AutoDock-based incremental protocol (DINC) that addresses the limitations of AutoDock's standard protocol by enabling improved docking of large ligands. Instead of docking a large ligand to a target protein in one single step as done in the standard protocol, our protocol docks the large ligand in increments. In this paper, we present three detailed examples of docking using DINC and compare the docking results with those obtained using AutoDock's standard protocol. We summarize the docking results from an extended docking study that was done on 73 protein-ligand complexes comprised of large ligands. We demonstrate not only that DINC is up to 2 orders of magnitude faster than AutoDock's standard protocol, but that it also achieves the speed-up without sacrificing docking accuracy. We also show that positional restraints can be applied to the large ligand using DINC: this is useful when computing a docked conformation of the ligand. Finally, we introduce a webserver for docking large ligands using DINC. Docking large ligands using DINC is significantly faster than AutoDock's standard protocol without any loss of accuracy. Therefore, DINC could be used as an alternative protocol for docking large ligands. DINC has been implemented as a webserver and is available at http://dinc.kavrakilab.org. Applications such as therapeutic drug design, rational vaccine design, and others involving large ligands could benefit from DINC and its webserver implementation.