Web Release Date: February 2,
Knowledge-Based Interaction Fingerprint Scoring: A Simple Method for Improving the Effectiveness of Fast Scoring Functions
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Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom, Department of Information Studies, University of Sheffield, Sheffield S1 4DP, United Kingdom, and GlaxoSmithKline Medicines Research Centre, Computational and Structural Sciences, Stevenage, Hertfordshire SG1 2NY, United Kingdom
Received September 23, 2005
Abstract:
A new method for the postprocessing of docking outputs has been developed, based on encoding putative 3D binding modes (docking solutions) as ligand-protein interactions into simple bit strings, a method analogous to the structural interaction fingerprint. Instead of employing traditional scoring functions, the method uses a series of new, knowledge-based scores derived from the similarity of the bit strings for each docking solution to that of a known reference binding mode. A GOLD docking study was carried out using the Bissantz estrogen receptor antagonist set along with the new scoring method. Superior recovery rates, with up to 2-fold enrichments, were observed when the new knowledge-based scoring was compared to the GOLD fitness score. In addition, top ranking sets of molecules (actives and potential actives or decoys) were structurally diverse with low molecular weights and structural complexities. Principal component analysis and clustering of the fingerprints permits the easy separation of active from inactive binding modes and the visualization of diverse binding modes.
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