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

Journal of Computer-aided Molecular Design
Darryl ReidAniko Simon

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.

References

Dec 1, 1995·Journal of Computer-aided Molecular Design·G JonesR C Glen
Apr 13, 2000·Journal of Chemical Information and Computer Sciences·M Wagener, van Geerestein VJ
Apr 13, 2000·Journal of Chemical Information and Computer Sciences·F Csizmadia
Jun 21, 2001·Journal of Chemical Information and Computer Sciences·M M HannG Harper
Oct 18, 2001·Journal of Chemical Information and Computer Sciences·G HarperA R Leach
Aug 12, 2003·Proteins·Marcel L VerdonkRichard D Taylor
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Jun 9, 2004·Journal of Molecular Graphics & Modelling·Timothy Clark
Jul 28, 2005·Journal of Chemical Information and Modeling·Jamal C SaehDavid A Cosgrove
Sep 29, 2006·Journal of Medicinal Chemistry·Tuan A Pham, Ajay N Jain
Dec 7, 2006·Journal of Computer-aided Molecular Design·Demetri T MoustakasRobert C Rizzo
Dec 13, 2006·Journal of Medicinal Chemistry·Niu HuangJohn J Irwin
Jan 5, 2007·Journal of Medicinal Chemistry·Paul C D HawkinsAnthony Nicholls
Jan 6, 2007·Journal of Computer-aided Molecular Design·Beining ChenNikolaus Stiefl
Feb 10, 2007·Journal of Chemical Information and Modeling·Jean-François Truchon, Christopher I Bayly
Jun 27, 2007·Journal of Chemical Information and Modeling·Georgia B McGaugheyWendy D Cornell

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Citations

Nov 15, 2011·Journal of Computer-aided Molecular Design·Orr RavitzAniko Simon
Oct 22, 2013·Colloids and Surfaces. B, Biointerfaces·Zhaoyang DingXuejun Cao
Apr 2, 2011·Future Medicinal Chemistry·Michael C Hutter
Jul 21, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Woong-Hee ShinDaisuke Kihara
Mar 8, 2011·Drug Discovery Today·Sean EkinsJoel S Freundlich
Aug 18, 2010·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Bashir S Sadjad, Zsolt Zsoldos
Dec 30, 2014·Trends in Pharmacological Sciences·Yu-Chian Chen
Jan 19, 2017·Environmental Science & Technology·Ana M SotoMaricel V Maffini
Nov 20, 2015·Molecular Informatics·Christopher R ReynoldsMichael J E Sternberg
Apr 2, 2019·Journal of Biomolecular Structure & Dynamics·Apeksha ShrivastavaMymoona Akhter
May 1, 2009·Journal of Chemical Information and Modeling·Markus Krier, Michael C Hutter
May 13, 2009·Journal of Chemical Information and Modeling·Sebastian G Rohrer, Knut Baumann
Mar 3, 2012·The Journal of Physical Chemistry. B·Christopher R ReynoldsMichael J E Sternberg

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