Comparison of Fingerprint-Based Methods for Virtual Screening Using Multiple Bioactive Reference Structures

Jérôme Hert, Peter Willett,* and David J. Wilton
Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
Pierre Acklin, Kamal Azzaoui, Edgar Jacoby, and Ansgar Schuffenhauer
Novartis Institutes for BioMedical Research, Discovery Technology Centre, Compound Logistics and Properties Unit, CH-4002 Basel, Switzerland
J. Chem. Inf. Comput. Sci., 2004, 44 (3), pp 1177–1185
DOI: 10.1021/ci034231b
Publication Date (Web): February 20, 2004
Copyright © 2004 American Chemical Society
*

 Corresponding author e-mail:  p.willett@sheffield.ac.uk.

Abstract

Fingerprint-based similarity searching is widely used for virtual screening when only a single bioactive reference structure is available. This paper reviews three distinct ways of carrying out such searches when multiple bioactive reference structures are available:  merging the individual fingerprints into a single combined fingerprint; applying data fusion to the similarity rankings resulting from individual similarity searches; and approximations to substructural analysis. Extended searches on the MDL Drug Data Report database suggest that fusing similarity scores is the most effective general approach, with the best individual results coming from the binary kernel discrimination technique.

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History

  • Published In Issue May 24, 2004
  • Received October 24, 2003

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