Three-dimensional protein-ligand interaction scaling of two-dimensional fingerprints.
We introduce a computational scaling methodology that utilizes protein-ligand interaction information extracted from complex crystal structures to enrich similarity searching using structural fingerprints with compound class-specific information. Scaling factors are derived to emphasize fingerprint bit positions that result from interacting fragments of bound ligands and correspond to frequently occurring structural features. Through interaction-based scaling, this information is transferred to standard fingerprints of multiple reference compounds. In systematic search calculations, fingerprints scaled on the basis of three-dimensional information are found to produce higher recall rates of active compounds than alternative types of scaled and non-scaled fingerprints.
Department of Life Science Informatics, Rheinische Friedrich-Wilhelms-Universität Bonn, Germany.
Lu
L
Tan
Martin
M
Vogt
Jürgen
J
Bajorath
D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008024:Ligands; D011506:Proteins