Docking to multiple pockets or ligand fields for screening, activity prediction and scaffold hopping

Future Med Chem. 2014;6(16):1741-55. doi: 10.4155/fmc.14.113.


Background: Two recent technological advances dramatically reducing the rate of false-negatives in activity prediction by docking flexible 3D models of compounds include multi-conformational docking (mPockDock) and the docking of candidates to atomic property fields derived by co-crystallized ligands (mApfDock).

Results: The mApfDock and mPockDock provide the AUC of 90.4 and 83.8%, respectively. The mApfDock gave better performance when compounds required large induced-fit pocket changes unseen in crystallography, whereas the mPockDock is superior when the co-crystallized ligands do not represent sufficient chemical and binding location diversity.

Conclusion: Both approaches proved to be efficient for scaffold hopping; they are complementary when the coverage of the co-crystallized complexes is poor but become convergent when the complexes are diverse enough.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Ligands
  • Molecular Docking Simulation*


  • Ligands