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.

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