Optimizing Fragment and Scaffold Docking by Use of Molecular Interaction Fingerprints
- 9 December 2006
- journal article
- Published by American Chemical Society (ACS) in Journal of Chemical Information and Modeling
- Vol. 47 (1), 195-207
- https://doi.org/10.1021/ci600342e
Abstract
Protein-ligand interaction fingerprints have been used to postprocess docking poses of three ligand data sets: a set of 40 low-molecular-weight compounds from the Protein Data Bank, a collection of 40 scaffolds from pharmaceutically relevant protein ligands, and a database of 19 scaffolds extracted from true cdk2 inhibitors seeded in 2230 scaffold decoys. Four popular docking tools (FlexX, Glide, Gold, and Surflex) were used to generate poses for ligands of the three data sets. In all cases, scoring by the similarity of interaction fingerprints to a given reference was statistically superior to conventional scoring functions in posing low-molecular-weight fragments, predicting protein-bound scaffold coordinates according to the known binding mode of related ligands, and screening a scaffold library to enrich a hit list in true cdk2-targeted scaffolds.Keywords
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