Structure-based protein–ligand interaction fingerprints for binding affinity prediction

Binding affinity prediction (BAP) using protein–ligand complex structures is crucial to computer-aided drug design, but remains a challenging problem. To achieve efficient and accurate BAP, machine-learning scoring functions (SFs) based on a wide range of descriptors have been developed. Among those descriptors, protein–ligand interaction fingerprints (IFPs) are competitive due to their simple representations, elaborate profiles of key interactions and easy collaborations with machine-learning algorithms. In this paper, we have adopted a building-block-based taxonomy to review a broad range of IFP models, and compared representative IFP-based SFs in target-specific and generic scoring tasks. Atom-pair-counts-based and substructure-based IFPs show great potential in these tasks.