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

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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.

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Authors and Affiliations

  1. SimBioSys Inc., 135 Queen’s Plate Drive, Suite 520, Toronto, ON, Canada, M9W 6V1

    Darryl Reid, Bashir S. Sadjad, Zsolt Zsoldos & Aniko Simon

Authors
  1. Darryl Reid
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  2. Bashir S. Sadjad
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  3. Zsolt Zsoldos
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  4. Aniko Simon
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Corresponding author

Correspondence to Aniko Simon.

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SimBioSys Inc.—http://www.simbiosys.ca

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Reid, D., Sadjad, B.S., Zsoldos, Z. et al. LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening. J Comput Aided Mol Des 22, 479–487 (2008). https://doi.org/10.1007/s10822-007-9164-5

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  • DOI: https://doi.org/10.1007/s10822-007-9164-5

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