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[News]
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Can we trust docking results?
Sept 2010 IBM Systems and Technology Group releases a white paper with eHiTS and Cell
Oct 2008
EPA's ToxCastTM project will use SimBioSys' eHiTS as docking engine
Nov, 2007
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[Events]
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| 243rd ACS
Mar 25-29, 2012
San Diego, CA
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Spring meeting 2008 (2008-04-24)
Lilly UK, Windlesham, Surrey
LASSO - ligand activity by surface similarity order: a new tool for ligand based virtual screening applied to 18 million structures
Zsolt Zsoldos (1), Aniko Simon (1), A. Peter Johnson (2), Antony Williams (3)
(1) SimBioSys Inc., 135 Queen's Plate Dr, Unit 520, Toronto, ON M9W 6V1, Canada
(2) School of Chemistry, University of Leeds, Leeds, LS2 9JT, United Kingdom
(3) ChemZoo Inc., Wake Forest, NC, USA
Abstract:
LASSO is a similarity searching tool that uses descriptors to find molecules with diverse chemical scaffolds but similar surface properties. Based on the idea that ligands must have surface properties compatible with the target site in order to bind, LASSO uses a descriptor using 23 different surface point types, ranging from hydrogen bond donors/acceptor, to hydrophobic sites, to pi-stacking interactions. This descriptor contains no 2D skeletal information about the molecule, no 3D geometrical relationships (shape) and very little volume information. However it is this "fuzziness" that allows LASSO to perform well as a scaffold hopping tool. LASSO will retrieve molecules, from a screened database, that have similar surface properties to those of a query set of known actives, regardless of the underlying scaffolds.
ChemSpider is a free access online database of over 18 million molecules provided as the basis of a structure centric community for chemists. LASSO has been applied to provide the virtual screening results for 40 target receptor families taken from the Database of Useful Decoys (DUD) and chosen to cover a wide range of receptor classes due to their interest in drug discovery. Similarity screening was performed on the full ChemSpider database across all targets and the similarity scores for each structure/target pair has been made available via the ChemSpider website providing a similarity score (based on surface properties) relative to actives of each of the 40 target receptors. In addition to allowing instant ranking results for your particular target of interest (retrieving molecules that are likely to be active for your receptor) this matrix of screening results can be used to find molecules that have high predicted affinity for your target but low predicted affinity for all other targets. Performing such searches promises to improve selectivity and can be a guide to reducing toxicity concerns. This presentation will provide an overview of the technology underlying both LASSO and ChemSpider and discuss the value of this offering to scientists in identifying potential leads via this virtual screening approach. We will discuss validation of the approach and early results from providing such information to the public.
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Full Presentation
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