Utilizing Target–Ligand Interaction Information in Fingerprint Searching for Ligands of Related Targets
Lu Tan, Jürgen Bajorath · Chemical Biology & Drug Design · 2009
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.