Harnessing systematic protein–ligand interaction fingerprints for drug discovery

Abstract

Determining protein-ligand interaction characteristics and mechanisms is crucial to the drug discovery process. Here, we review recent progress and successful applications of a systematic protein-ligand interaction fingerprint (IFP) approach for investigating proteome-wide protein-ligand interactions for drug development. Specifically, we review the use of this IFP approach for revealing polypharmacology across the kinome, predicting promising targets from which to design allosteric inhibitors and covalent kinase inhibitors, uncovering the binding mechanisms of drugs of interest, and demonstrating resistant mechanisms of specific drugs. Together, we demonstrate that the IFP strategy is efficient and practical for drug design research for protein kinases as targets and is extensible to other protein families.