Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking

A key metric to assess molecular docking remains ligand
enrichment
against challenging decoys. Whereas the directory of useful decoys
(DUD) has been widely used, clear areas for optimization have emerged.
Here we describe an improved benchmarking set that includes more diverse
targets such as GPCRs and ion channels, totaling 102 proteins with
22886 clustered ligands drawn from ChEMBL, each with 50 property-matched
decoys drawn from ZINC. To ensure chemotype diversity, we cluster
each target’s ligands by their Bemis–Murcko atomic frameworks.
We add net charge to the matched physicochemical properties and include
only the most dissimilar decoys, by topology, from the ligands. An
online automated tool (http://decoys.docking.org) generates
these improved matched decoys for user-supplied ligands. We test this
data set by docking all 102 targets, using the results to improve
the balance between ligand desolvation and electrostatics in DOCK
3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org.

评估分子对接性能的关键指标之一，仍是针对高难度诱饵的配体富集效果。此前广泛使用的有用诱饵数据库（Directory of Useful Decoys, DUD）已显现出明确的优化空间。本文描述了一款改进型基准数据集，其包含更多样化的靶标，如G蛋白偶联受体（GPCRs）与离子通道，共计102个蛋白质靶点；数据集涵盖源自ChEMBL数据库的22886个聚类配体，每个配体对应50个从ZINC数据库中筛选出的性质匹配诱饵。为保证化学型多样性，我们基于贝米斯-默科原子骨架（Bemis–Murcko atomic frameworks）对每个靶标的配体进行聚类。我们新增净电荷作为匹配的理化性质之一，并仅选取与配体拓扑结构差异最大的诱饵作为匹配集。一款在线自动化工具（http://decoys.docking.org）可为用户提供的配体生成此类改进型匹配诱饵。我们通过对全部102个靶点开展分子对接以测试该数据集，并利用测试结果优化了DOCK 3.6软件中配体去溶剂化与静电作用间的平衡。完整的DUD-E基准数据集可在http://dude.docking.org免费获取。