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Journal of Computer-Aided Molecular Design

, Volume 23, Issue 3, pp 143–152 | Cite as

An improved scoring function for suboptimal polar ligand complexes

  • Giovanni Cincilla
  • David Vidal
  • Miquel PonsEmail author
Article

Abstract

Learning strategies can be used to improve the efficiency of virtual screening of very large databases. In these strategies new compounds to be screened are selected on the basis of the results obtained in previous stages, even if truly good ligands have not yet been identified. This approach requires that the scoring function used correctly predicts the energy and geometry of suboptimal complexes, i.e. weak complexes that are not the final solution of the screening but help direct the search toward the most productive regions of chemical space. We show that a small modification in the treatment of the solvation of polar atoms corrects the tendency of the original Autodock 3.0 scoring function to bury ligand polar atoms away from solvent, even if no complementary groups are present in the target and improves the performance of Autodock 3.0 and 4.0 in reproducing the experimental docking energies of weak complexes, resembling the suboptimal complexes encountered in the intermediate stages of virtual screening.

Keywords

Docking Drug design Virtual screening Scoring function Solvation 

Notes

Acknowledgments

This work has been supported by funds from the Spanish Ministerio de Educación y Ciencia-FEDER BIO2004-5436 and BIO2007-63458 and the Generalitat de Catalunya. DV and GC gratefully acknowledge predoctoral grants from the Spanish Ministerio de Educación y Ciencia.

Supplementary material

10822_2008_9246_MOESM1_ESM.doc (392 kb)
(DOC 392 kb)

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Giovanni Cincilla
    • 1
    • 2
  • David Vidal
    • 1
    • 2
    • 3
  • Miquel Pons
    • 1
    • 2
    Email author
  1. 1.Laboratory of Biomolecular NMRInstitute for Research in Biomedicine, Science Research ParkBarcelonaSpain
  2. 2.Departament de Química OrgànicaUniversitat de BarcelonaBarcelonaSpain
  3. 3.CHEMOTARGETS S.L.BarcelonaSpain

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