Journal of Computer-Aided Molecular Design

, Volume 26, Issue 8, pp 921–934 | Cite as

Virtual fragment screening: exploration of MM-PBSA re-scoring

  • Sameer Kawatkar
  • Demetri Moustakas
  • Matthew Miller
  • Diane Joseph-McCarthy
Article

Abstract

An NMR fragment screening dataset with known binders and decoys was used to evaluate the ability of docking and re-scoring methods to identify fragment binders. Re-scoring docked poses using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) implicit solvent model identifies additional active fragments relative to either docking or random fragment screening alone. Early enrichment, which is clearly most important in practice for selecting relatively small sets of compounds for experimental testing, is improved by MM-PBSA re-scoring. In addition, the value in MM-PBSA re-scoring of docked poses for virtual screening may be in lessening the effect of the variation in the protein complex structure used.

Keywords

Virtual screening Fragment screening Prostaglandin D2 synthase MM-PBSA Docking 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Sameer Kawatkar
    • 1
  • Demetri Moustakas
    • 1
  • Matthew Miller
    • 1
  • Diane Joseph-McCarthy
    • 1
  1. 1.Infection Innovative Medicines Unit, Chemistry DepartmentAstraZenecaWalthamUSA

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