Knowledge-based interaction fingerprint scoring: a simple method for improving the effectiveness of fast scoring functions.
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.
Mpamhanga
Chidochangu P
CP
Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
Chen
Beining
B
McLay
Iain M
IM
Willett
Peter
P
D016000:Cluster Analysis; D003198:Computer Simulation; D019992:Databases as Topic; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding; D020849:Raloxifene Hydrochloride / Q000737:chemistry
D047628:Estrogen Receptor alpha; D008024:Ligands; D020849:Raloxifene Hydrochloride