Utilizing target-ligand interaction information in fingerprint searching for ligands of related targets.
Protein-ligand interaction information is captured by determination of interacting fragments (IF) of ligands available in complex X-ray structures. From IF, fingerprints (IF-FP) are calculated for similarity searching. Previously, we have shown that IF-FP often produce higher search performance than general structural fragment- or key-type fingerprints. In this study, we introduce the transfer of target-ligand interaction information from one target to a related one for which no structural information is available. Thus, IFs from a crystallographic target B-ligand complex are incorporated into structural key fingerprints of known ligands for target A. Similarity searching using these IF transfer fingerprints (IF-TFP) is shown to further increase the search performance of conventional ligand fingerprints. Thus, interaction information can be transferred between related targets in order to support ligand-based fingerprint search calculations for targets for which no structural information is currently available.
Tan
Lu
L
Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, D-53113 Bonn, Germany.
Bajorath
Jürgen
J
D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004791:Enzyme Inhibitors / Q000737:chemistry; D008024:Ligands; D008084:Lipoxygenase / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D054852:Small Molecule Libraries
D004791:Enzyme Inhibitors; D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries; C095864:lipoxygenase 3; D008084:Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase