Journal of Computer-Aided Molecular Design

, Volume 22, Issue 6, pp 479–487

LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening


  • Darryl Reid
    • SimBioSys Inc.
  • Bashir S. Sadjad
    • SimBioSys Inc.
  • Zsolt Zsoldos
    • SimBioSys Inc.
    • SimBioSys Inc.

DOI: 10.1007/s10822-007-9164-5

Cite this article as:
Reid, D., Sadjad, B.S., Zsoldos, Z. et al. J Comput Aided Mol Des (2008) 22: 479. doi:10.1007/s10822-007-9164-5


Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.


Conformation independent QSAR descriptorScaffold hoppingVirtual screeningLigand based screening

Supplementary material

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© Springer Science+Business Media B.V. 2008