Ensemble-based docking: From hit discovery to metabolism and toxicity predictions

Wilfredo Evangelista, Rebecca L. Weir, Sally R. Ellingson, Jason B. Harris, Karan Kapoor, Jeremy C. Smith, Jerome Baudry

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.

Original languageEnglish
Pages (from-to)4928-4935
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number20
StatePublished - 2016

Bibliographical note

Funding Information:
The results presented here describe the work performed computationally by laboratories in the UT/ORNL Center for Molecular Biophysics. We express our profound gratitude to our experimental collaborators (co-authors on the respective publications) who have performed the experimental work on two of these projects: the Center for Environmental Biotechnology at the University of Tennessee for the PCB-30 estrogenization pathway project, and Shifa Biomedical and the laboratory of Dr. Cynthia Peterson at the University of Tennessee for the FXa:FVa project. This work was financially supported by the University of Tennessee Governor Chair program for J.C.S. and by a start up grant from the Department of Biochemistry and Cellular and Molecular Biology to J.B.; as well as by the National Institutes of Health 1R43HL11426 for the FXa:FVa project to J.B., and by the National Institutes of Health 1KL2RR031974 and the Department of Energy for the development of VinaMPI to J.B. and J.C.S.

Publisher Copyright:
© 2016 Elsevier Ltd


  • Computational drug discovery
  • Docking
  • Drug discovery
  • Hit discovery
  • Lead discovery
  • Toxicity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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