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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)789-801
Number of pages13
JournalJournal of Computer-Aided Molecular Design
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2010

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Keywords

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

ASJC Scopus subject areas

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

Cite this

Armstrong, M. S., Morris, G. M., Finn, P. W., Sharma, R., Moretti, L., Cooper, R. I., & Richards, W. G. (2010). ElectroShape: Fast molecular similarity calculations incorporating shape, chirality and electrostatics. Journal of Computer-Aided Molecular Design, 24(9), 789-801. https://doi.org/10.1007/s10822-010-9374-0