Journal of Computer-Aided Molecular Design

, Volume 24, Issue 9, pp 789–801

ElectroShape: fast molecular similarity calculations incorporating shape, chirality and electrostatics

  • M. Stuart Armstrong
  • Garrett M. Morris
  • Paul W. Finn
  • Raman Sharma
  • Loris Moretti
  • Richard I. Cooper
  • W. Graham Richards
Article

Abstract

We present ElectroShape, a novel ligand-based virtual screening method, that combines shape and electrostatic information into a single, unified framework. Building on the ultra-fast shape recognition (USR) approach for fast non-superpositional shape-based virtual screening, it extends the method by representing partial charge information as a fourth dimension. It also incorporates the chiral shape recognition (CSR) method, which distinguishes enantiomers. It has been validated using release 2 of the Directory of useful decoys (DUD), and shows a near doubling in enrichment ratio at 1% over USR and CSR, and improvements as measured by Receiver Operating Characteristic curves. These improvements persisted even after taking into account the chemotype redundancy in the sets of active ligands in DUD. During the course of its development, ElectroShape revealed a difference in the charge allocation of the DUD ligand and decoy sets, leading to several new versions of DUD being generated as a result. ElectroShape provides a significant addition to the family of ultra-fast ligand-based virtual screening methods, and its higher-dimensional shape recognition approach has great potential for extension and generalisation.

Keywords

Molecular similarity Molecular descriptors Ligand-based virtual screening Drug design Chirality chemotypes 

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • M. Stuart Armstrong
    • 1
  • Garrett M. Morris
    • 1
  • Paul W. Finn
    • 1
  • Raman Sharma
    • 1
  • Loris Moretti
    • 2
  • Richard I. Cooper
    • 1
  • W. Graham Richards
    • 2
  1. 1.InhibOxOxfordUK
  2. 2.Department of Chemistry, InhibOx LaboratoryUniversity of OxfordOxfordUK

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