Structure‐Based Approaches to Target Fishing and Ligand Profiling

Chemogenomics is an emerging interdisciplinary field aiming at identifying all possible ligands of all possible targets. If one groups targets in columns and ligands in rows, chemogenomic approaches to drug discovery just fill the interaction matrix. Since experimental data do not suffice, several computational methods are currently actively developed to supplement time‐consuming and costly experiments. They are either designed to fill rows and thus profile a ligand towards a heterogeneous set of targets (target profiling) or to fill columns and thus identify novel ligands for an existing target (standard virtual screening). At the interface of both strategies are now true chemogenomic computational methods filling well defined areas in the matrix. The present review will focus on (protein) structure‐based approaches and illustrates major advances in this novel exciting field which is supposed to massively impact rational drug design in the next decade.