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