BACKGROUND 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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DINC：一种新的基于 AutoDock 的协议，用于对接大配体。

背景使用流行的程序AutoDock，具有6个或更少可旋转键的小配体的计算机辅助对接相当快速和准确。然而，使用 AutoDock 推荐的标准对接协议对接大配体不太准确，计算速度也很慢。结果 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)，该协议通过改进大配体的对接来解决 AutoDock 标准协议的局限性。我们的协议不是像标准协议那样在一个步骤中将大配体与目标蛋白质对接，而是以增量方式对接大配体。在本文中，我们展示了三个使用 DINC 对接的详细示例，并将对接结果与使用 AutoDock 标准协议获得的结果进行了比较。我们总结了对由大配体组成的 73 种蛋白质-配体复合物进行的扩展对接研究的对接结果。我们证明，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。我们还表明可以使用 DINC 将位置限制应用于大配体：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 对接大型配体的网络服务器。结论 使用 DINC 对接大型配体的速度明显快于 AutoDock 的标准协议，而不会损失任何准确性。因此，DINC 可用作对接大配体的替代方案。DINC 已作为网络服务器实施，可从 http://dinc.kavrakilab 获得。组织。诸如治疗药物设计、合理疫苗设计以及其他涉及大配体的应用程序都可以从 DINC 及其网络服务器实施中受益。