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

Authors

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

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

Abstract

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.

Keywords

Conformation independent QSAR descriptorScaffold hoppingVirtual screeningLigand based screening

Supplementary material

Copyright information

© Springer Science+Business Media B.V. 2008