Systematic exploitation of multiple receptor conformations for virtual ligand screening

Giovanni Bottegoni, Walter Rocchia, Manuel Rueda, Ruben Abagyan, Andrea Cavalli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario.

Original languageEnglish
Article numbere18845
JournalPLoS ONE
Issue number5
Publication statusPublished - 24 May 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


Dive into the research topics of 'Systematic exploitation of multiple receptor conformations for virtual ligand screening'. Together they form a unique fingerprint.

Cite this