Avalanche for shape and feature-based virtual screening with 3D alignment

David J. Diller, Nancy D. Connell, William J. Welsh

Research output: Contribution to journalArticle

Abstract

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

Original languageEnglish (US)
Pages (from-to)1015-1024
Number of pages10
JournalJournal of Computer-Aided Molecular Design
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Keywords

  • Antibacterial drug discovery
  • Shape matching
  • Three dimensional alignment
  • Virtual screening

ASJC Scopus subject areas

  • Drug Discovery
  • Computer Science Applications
  • Physical and Theoretical Chemistry

Fingerprint Dive into the research topics of 'Avalanche for shape and feature-based virtual screening with 3D alignment'. Together they form a unique fingerprint.

  • Cite this