Multi-conformer ensemble docking to difficult protein targets

Sally R. Ellingson, Yinglong Miao, Jerome Baudry, Jeremy C. Smith

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Large-scale ensemble docking is investigated using five proteins from the Directory of Useful Decoys (DUD, for which docking to crystal structures has proven difficult. Molecular dynamics trajectories are produced for each protein and an ensemble of representative conformational structures extracted from the trajectories. Docking calculations are performed on these selected simulation structures and ensemble-based enrichment factors compared with those obtained using docking in crystal structures of the same protein targets or random selection of compounds. Simulation-derived snapshots are found with improved enrichment factors that increase the chemical diversity of docking hits for four of the five selected proteins. A combination of all the docking results obtained from molecular dynamics simulation followed by selection of top-ranking compounds appears to be an effective strategy for increasing the number and diversity of hits when using docking to screen large libraries of chemicals against difficult protein targets.

Original languageEnglish
Pages (from-to)1026-1034
Number of pages9
JournalJournal of Physical Chemistry B
Issue number3
StatePublished - Jan 22 2015

Bibliographical note

Publisher Copyright:
© 2014 American Chemical Society.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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