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

35 Scopus citations

Abstract

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
Volume24
Issue number20
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • 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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