Improving the accuracy of ultrafast ligand-based screening: incorporating lipophilicity into ElectroShape as an extra dimension
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In a previous paper, we presented the ElectroShape method, which we used to achieve successful ligand-based virtual screening. It extended classical shape-based methods by applying them to the four-dimensional shape of the molecule where partial charge was used as the fourth dimension to capture electrostatic information. This paper extends the approach by using atomic lipophilicity (alogP) as an additional molecular property and validates it using the improved release 2 of the Directory of Useful Decoys (DUD). When alogP replaced partial charge, the enrichment results were slightly below those of ElectroShape, though still far better than purely shape-based methods. However, when alogP was added as a complement to partial charge, the resulting five-dimensional enrichments shows a clear improvement in performance. This demonstrates the utility of extending the ElectroShape virtual screening method by adding other atom-based descriptors.
KeywordsMolecular similarity Molecular descriptors Ligand-based virtual screening Drug design Lipophilicity Electrostatics
- 6.Chemical Computing Group, Montreal, Canada, MOE 2008.10, http://www.chemcomp.com